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Notes: Abstract To evaluate the development of renal hypoxia during hemorrhagic shock, fourteen dogs were induced in this study. The animals were divided equally into a group in which mean arterial pressure (MAP) was kept at 50 mmHg (group 1), and into another where MAP was kept at 40 mmHg for 180 mim (group 2). Renal tissue gas tensions were determined by a mass spectrometer. In the 50-mmHg group, renal tissue oxygen tension (PrO 2) dropped for 15 min following hemorrhage, remained constant for 90 min, then fell further for 150 min before a plateau was established. In the 40-mmHg group, the PrO 2 dropped for 90 min before reaching a plateau. The second PrO 2 decline occurred at the same level in both the 50-mmHg group and the 40-mmHg group. The point at which the same PrO 2 level occurred for each group suggests the cessation of oxygen consumption and the conditions of renal hypoxia. It is assumed that renal hypoxia occurs in 120 min at a MAP of 50-mmHg and in 60 min at a MAP of 40 mmHg. (Murakawa K, Izumi R, Kobayashi A: Renal tissue gas tentions during hemorrhagic shock. J Anesth 3: 10–15, 1989)

Notes: Summary Mercury concentration in intraoral air and urine of seven females with dental amalgam was measured before and after intake of one hard-boiled egg. A considerable decrease in mercury concentration in intraoral air was found. Twenty women with about equal dental amalgam status, with or without subjective symptoms related to dental amalgam, were also studied. Mercury concentrations in intraoral air and urine were measured. For all the 27 women the basal intraoral air concentration of mercury ranged over 0.6–10.4 μg/m3 (median value 4.3 μg/m3). This corresponds to a release of 0.02–0.38 ng/s (median value 0.16 ng/s). In urine, the mercury concentration varied from 〈 0.8–6.9 μg/g creatinine (median value 1.9 μg/g creatinine). Data from both parameters were significantly correlated to the total number of teeth areas with dental amalgam. Protein values in urine indicated no renal damage. Maximum concentrations of mercury vapour in intraoral air for the 27 women who had chewed chewing gum for 5 min varied between 2–60 μg Hg/m3 (median value 19 μg Hg/m3). This corresponds to 0.07–2.20 ng Hg/s and a median value of 0.70 ng Hg/s.

Notes: Summary Renal sympathetic nerve varicosities possess a variety of receptors which when activated by appropriate agonists can modulate noradrenaline release at the local level of the kidney. Thus, activation of prejunctional α1- and α2-adrenoceptors, prostaglandin (PG), dopamine, adenosine and serotonin receptors inhibits, whereas activation of prejunctionalβ 2-adrenoceptors and angiotensin (A) II receptors enhances renal noradrenaline release. Moreover, neuronally released noradrenaline itself activates prejunctional inhibitory α1- and α2-adrenoceptors forming a “negative feedback loop” of its own release (autoinhibition). PGE2 and adenosine locally formed in the kidney by renal nerve stimulation inhibits noradrenaline release through activation of their specific prejunctional receptor system (transjunctional inhibition).

Notes: Summary Recently, a mutant rat strain was described with a genetic defect for the biliary excretion of organic anions (TR− rats). To determine the possible heterogeneity of the transport systems in liver, intestine and kidney we investigated the transport of the anion 1-naphthol-β-d-glucuronide (1-NG) in isolated vascularly perfused organ preparations of the rat liver, intestine and kidney of both Wistar rats and TR− rats. 1-NG was administered as such (liver and kidney experiments) or formed intracellularly from 1-naphthol (1-N) (liver and gut experiments). Independent of the type of exposure to 1-NG, the biliary excretion was considerably impaired in TR− rats. In the intestine the total appearance and the vascular/luminal distribution pattern of 1-NG were not significantly different from the values in control rats. Furthermore, no significant disturbance was found with respect to the renal clearance of 1-NG in the TR− rat when compared with the Wistar rat. Thus, the genetic defect in the TR− rat is restricted to an impaired hepatobiliary excretion of 1-NG and does not affect the excretory systems of the intestine and kidney. These results suggest that the excretion of 1-NG by the liver, intestine and kidney involves distinct organ-specific transport systems.

Notes: Summary Following renal ischemia under protection, the perfusion of the tubular system increases concomitant to the rise of GFR. The transport into urine of enzymes entering the tubular lumen due to ischemic injury is dependent on tubular flow. Thus, we examined if in the early post-ischemic phase urinary enzyme determinations can contribute to the evaluation of a changing tubular washout. Canine kidneys were perfused with different protective solutions and subsequently rendered ischemic. From the beginning of reperfusion the endogenous creatinine clearance, the urine minute volume and the urinary LDH-concentration were determined. The urinary LDH-concentration allowed only a rough assessment of renal ischemic damage. The adjustment of the urinary LDH amounts to the GFR resulted in a better graduation according to the ischemic stress. With such a standardized LDH parameter the urinary LDH release was somewhat lower on the average when L-aspartate was added to the HTK solution in place of chloride. In conclusion, during the early postischemic recovery after renal protection the examination of the urinary enzyme release may be a useful diagnostic means for the assessment of the extent of the ischemic injury if an appropriate frame of reference is applied.

Notes: Summary In the present study, the diameters of afferent and efferent arterioles of kidneys from spontaneously hypertensive rats (SHR) were evaluated and compared with those from Wistar Kyoto rats (WKY) using a vascular cast model. At 4 weeks of age, the blood pressure was slightly higher in SHR than in WKY (124±1 vs 116±7 mmHg, ns). The diameters of afferent arterioles in SHR were smaller than those in WKY (10.3±0.6 vs 12.3±0.7 µm,P〈0.001), whereas the diameters of efferent arterioles were comparable in the two strains. At 20 weeks of age, the blood pressure was markedly elevated in SHR than in WKY (192±5 vs 140±4 mmHg,P〈0.001). The diameters of afferent arterioles in SHR at this age were much smaller than those in WKY (14.3±0.5 vs 17.1±0.6 µm,P〈0.01). The diameters of efferent arterioles in SHR were, however, larger than those in WKY (15.4±l.2 vs 12.9±0.4 µm,P〈 0.05). The net effect of these changes in arteriolar size helps to maintain normal intraglomerular pressure and to protect glomeruli from damage due to hypertension.

Notes: Summary The addition of the dissaccharides maltose (10, 20, 30 mM) and sucrose (30, 60 mM) to Bretschneider's organ protective HTK solution was evaluated to improve renal protection by an enhanced glycolytic energy supply. Canine kidneys were perfused for 8 min with either HTK solution or HTK solution containing additional disaccharides. After nephrectomy the kidneys were incubated at 25°C and metabolic parameters were determined at regular intervals. Maltose and sucrose are slowly cleaved during renal ischemia but maltose distinctly faster than sucrose. Maltose increases intraischemic ATP supply. However, 30 mM maltose was no better than 10 mM. 60 mM sucrose was about as effective for glycolysis as 10 mM maltose. However, possibly due to fructose release there was an accelerated decrease of adenine nucleotides with sucrose. Although fructose enters glycolysis it seems to have negative side-effects. Hence, probably neither sucrose nor fructose are appropriate for renal substrate supply during ischemia.

Notes: Summary Amino acids are known to increase glomerular filtration rate (GFR). There is also an early resumption of filtration following 2-h renal ischemic stress under protection by histidine-buffered histidine-tryptophanketoglutarate solution (HTK), possibly due in part to an amino acid effect. Hence, we have examined the possibility of further enhancing the postischemic GFR by adding 32 (ASP I; 4 mM Mg2+) or 36 (ASP II; 6 mM Mg2+) mM l-aspartate (asp) or 32 mM dl-aspartate (ASP III) to the HTK solution in place of chloride. After infusion of 500 ml 5% glucose, canine kidneys were protected by an 8-min perfusion with HTK (n = 5), ASP I (n = 4), ASP II (n = 5) or ASP III-solution (n = 3). The subsequent ischemia lasted for 2 h at 27–31°C. During reperfusion, both GFR and filtration fraction (FF) were higher in kidneys protected byl-aspartate-containing solutions. ASP III showed no improvement against HTK. An additional preischemic intraaortal application of HTK or ASP I solution just above the exit of the renal arteries prior to the intrinsic protective perfusion further raised the postischemic GFR. The present results suggest thatl-aspartate but also histidine may have favorable amino acid effects in renal protective solutions in addition to known positive effects of histidine.

Notes: Summary Human renal growth was studied in 60 kidneys (30 staged fetuses, ranging in age from 10 to 38 weeks post conception, WPC). The kidneys were measured for greatest length (L) and weight (W) and the data correlated to the gestational age by using the allometric method (Y = bXK). The equations of the growth curves are presented in the text.

Notes: Abstract In order to establish the characteristics of net renal transport and utilization of α-ketoglutarate (α-KG) in the rat, we have precisely quantified the renal blood flow, the urinary flow and the rates of α-KG delivery, filtration, reabsorption or secretion, excretion, uptake or production by an in vivo rat kidney preparation. In normal rats, α-KG uptake was higher than α-KG reabsorption at both endogenous and elevated plasma α-KG concentrations; thus, a net peritubular transport, which was the main supplier of α-KG to the renal cells, took place. Saturation of reabsorption and peritubular transport of α-KG occurred at blood α-KG concentrations about 30 and 150 times above normal, respectively. Acute metabolic acidosis was found to have no effect on renal handling of α-KG. At endogenous plasma α-KG concentrations, alkalosis converted net renal uptake into net renal production of α-KG resulting in addition of α-KG by the renal cells both to blood and to the luminal fluid. Elevation of blood α-KG concentration restored the renal uptake of α-KG. This uptake, which was entirely accounted for by the peritubular transport of α-KG, reached a maximum which was lower than that observed in normal and acidotic rats.

Notes: Summary We report on kidney structure and function in subterranean mammals of four chromosomal species (2n=52, 54, 58 and 60) belonging to the Spalax ehrenbergi superspecies, in relation to their speciation and adaptive radiation from mesic (2n=52) to xeric (2n=60) environments in Israel. Structural variables measured involved: (1) Relative Medullary Thickness, (RMT); (2) Relative Kidney Weight. (RKW); and (3) Percentage of Kidney out of Body Weight (PKW). Functional variables involved: (i) Urine Solid Concentration, (USC); and (ii) Urine Osmotic Concentration (UOC). The results for chromosomal species 2n=52, 54, 58 and 60 indicated nonsignificant increase southward for RMT, but displayed significant increase along the same transect for RKW, PKW, and USC. The UOC was significantly lower in mesic 2n=52 as compared to the other three species when experimental animals were fed in the laboratory on regular carrot food. However, protein stress food (soybean) and salt stress of 0.45 mol NaCl, caused significant, three and a half fold increase of UOC in 2n=52, 54 and 58; but four and a half fold increase in 2n=60, significantly higher than in the other three species. We conclude that both structurally and functionally, the kidneys differentiated adaptively during the Pleistocene evolution of S. ehrenbergi in Israel, in accordance with aridity stress and halophyte food resources towards the desert. Nevertheless, Spalax generally shows clear upper limits in kidney structural and functional capacities, preventing it from colonizing the true desert, south of the 100 mm isohyete.

Notes: Abstract A new automated biopsy technique is described for performing percutaneous renal biopsies in pediatric patients. The biopsy device (Bard Biopty Instrument) employs a relatively small needle (18 gauge). We believe this procedure offers a safer and more effective means of obtaining adequate renal tissue for pathological assessment in pediatric patients.

Notes: Summary The usefulness of real-time ultrasonography as a guidance method in performing percutaneous renal biopsy is evaluated on the basis of a series of 114 patients with diffuse nephropathies. Sufficient renal tissue for light microscopy was obtained in 102 patients (89.5%) and enough for electron microscopy in 93 patients (81.6%) and for fluorescence microscopy in 91 patients (79.8%). A final histological diagnosis was possible in 106 patients (93%). The high diagnostic rate, the reduction in the contraindications to the procedure, the lack of major postbiopsy complications, and the cost effectiveness probably make real-time ultrasound scanning the method of choice when performing renal biopsy in patients with diffuse nephropathies.

Notes: Summary An antibody to the 96 kD α-subunit of the Na+, K+ -ATPase from Bufo marinus has been used in immunostaining rat kidney and salivary glands. Intense staining was observed on basolateral membranes of distal tubules of the kidney and striated ducts of the three major salivary glands. Less intense staining was seen on the basolateral membranes of parotid acinar cells, but no staining was seen on the acinar cells of submandibular or sublingual glands. These sites of staining have been shown, by other methods, to posses substantial Na+, K+ -ATPase, indicating that the antibody recognizes antigenic determinants of the sodium pump highly conserved in the course of evolution. In addition, staining with this antibody was observed at the apical region of cells of the proximal straight tubule and of the papillary collecting duct in the kidney. Absorption studies suggest that the apical antigenic determinants are the same or closely related to each other but are distinct from basolateral antigenic determinants.

Notes: Summary The hydrolysis of 5′-AMP by 5′-nucleotidase is the main source of adenosine. In various tissues adenosine is a local mediator adjusting the organ work to the available energy. In the kidney it regulates renal hemodynamics, glomerular filtration rate and renin release via specific receptors of the arteriolar walls. By immunocytochemistry we identified interstitial and tubular sites of 5′-nucleotidase in the rat kidney. In the interstitium the enzyme was detected only in the cortical labyrinth, the compartment that comprises all arteriolar vessels besides other putative targets of adenosine. The 5′-nucleotidase-positive cells of the interstitium were identified as fibroblasts. The fibroblasts are in close contact with the tubules as well as with the vessels. Thus, any 5′-AMP released by the tubules into the interstitial space would be converted to adenosine in the direct vicinity of its assumed targets. Adenosine produced by tubular cells would hardly have access to its known targets, since 5′-nucleotidase is restricted to the luminal cell surface. Pathological events affecting the fibroblasts might influence renal function by modifying the interstitial adenosine production.

Notes: Summary Granulated epithelial cells at the vascular pole of the renal corpuscle, peripolar cells, have been found in the kidneys of five species of elasmobranchs, the little skate (Raja erinaced), the smooth dogfish shark (Mustelus canis), the Atlantic sharpnose shark (Rhizoprionodon terraenovae), the scalloped hammerhead shark (Sphryna lewini), and the cow-nosed ray (Rhinoptera bonasus). In a sixth elasmobranch, the spiny dogfish shark (Squalus acanthias), the peripolar cells could not be identified among numerous other granulated epithelial cells. The peripolar cells are located at the transition between the parietal epithelium of Bowman's capsule and the visceral epithelium (podocytes) of the glomerulus, thus forming a cuff-like arrangement surrounding the hilar vessels of the renal corpuscle. These cells may have granules and/or vacuoles. Electron microscopy shows that the granules are membrane-bounded, and contain either a homogeneous material or a paracrystalline structure with a repeating period of about 18 nm. The vacuoles are electron lucent or may contain remnants of a granule. These epithelial cells lie close to the granulated cells of the glomerular afferent arteriole. They correspond to the granular peripolar cells of the mammalian, avian and amphibian kidney. The present study is the first reported occurrence of peripolar cells in a marine organism or in either bony or cartilagenous fish.

Notes: Summary To clarify the structural base of immune response occurring in the kidney, we investigated the antigenic and functional properties of vascular endothelial cells. Peritubular capillary endothelial cells exhibited the same immuno-histochemical characteristics (OKM5-positive, HLA-DR-positive, Factor VIII/von Willebrand factor antigen-negative, Interleukin 1-positive) as a peripheral blood macrophage subset capable of presenting soluble antigens and triggering the autologous mixed lymphocyte reaction. On the other hand, endothelial cells of glomerular capillary loops, considered to be involved in blood coagulation, were OKM5-negative, HLA-DR-positive, Factor VIII/von Willebrand factor antigen-positive, Interleukin 1-positive. Thus the results of this study suggest that vascular endothelial cells in different anatomic compartments of the kidney express surface antigens heterogenously and may play different roles in the immune reaction.

Notes: Summary The interior of Bowman's capsules of rat kidneys has been examined by scanning electron microscopy, and a distinctive population of cells around the exposed vascular poles of glomerular tufts were identified. The cells were situated in the annular groove at the root of the glomerulus, between the parietal epithelial cells and the podocytes. These peripolar cells were dendritic cells with long processes embracing the glomerular arterioles. Up to three peripolar cells were present at each vascular pole and they were mainly distributed in the glomeruli of the outer third of the renal cortex. This first detailed study of the surface morphology of the glomerular peripolar cell supports the suggestion that changes in the diameter of the polar region of the glomerular tuft may cause variations in stretching of the cuff of peripolar cells, and hence modulation of their secretory activity.

Notes: Summary The ultrastructure of rat glomerular epithelial cells (podocytes) in kidney slices in vitro was examined using qualitative and quantitative electron microscopy. The kidney slices were cultured in Medium 199 with Hanks' salts in a 5% CO2/95% O2 environment for up to 14 days. Few changes in podocyte ultrastructure occurred in the first 12 h of culture, but by 24 h cell bodies were rounded, microvilli were present on all podocyte surfaces, and some foot processes had been replaced by flattened expanses of cytoplasm. These changes were more pronounced by 3 days, when some podocytes had developed pseudopodal extensions and appeared to be migrating from glomeruli onto the slice surface. Podocytes could still be identified after 8, 10 and 14 days of culture, although relatively few glomeruli remained at 14 days. Morphometric methods were used to analyse podocyte shape, volume and surface area during the first 4 days of culture. The most significant change involved loss of foot processes: the number of filtration slits per 100 μm of basement membrane decreased from 211.8 ± 15.0 (mean ± SD) at the commencement of culture, to 55.3 ± 22.6 after 2 days (P 〈 0.001). These data provide baseline information for in vitro studies on the effects of nephrotoxins on podocytes.

Notes: Summary Fifty-eight patients, aged 48–87 years, with impaired renal function and mean initial creatinine clearance of 52.1 mls/min were recruited to a 12-week open study of tenoxicam 20 mg/day for osteoarthrosis or rheumatoid arthritis. Renal function was mea sured before and after a brief run-in period when patients discontinued all nonsteroidal anti-inflammatory drugs, taking paracetamol alone, prior to monthly monitoring thereafter. Fifty-four% of patients completed the study, the others being withdrawn from lack of efficacy (17%), adverse events (24%) or both (5%). During the run-in period the mean creatinine clearance of 28 patients completing the trial improved to 64.7 mls/min and then dropped to 57.9 mls/min during the course of 12 weeks treatment with tenoxicam. Serial analysis of haematological and biochemical safety parameters showed no drug-induced change of significance. Twenty-three% of patients felt worse and 45% better at the end of treatment. Seventeen patients withdrew because of adverse events. These were normally gastrointestinal and always unrelated to further deterioration in renal function. Tenoxicam, 20 mg/day, can be given safely for a period of at least three months in patients with mild or moderate renal impairment.

Notes: Summary Specific binding sites for atrial natriuretic peptide (99–126) in different areas of normal human renal tissue were quantified by in vitro autoradiography. Our data represent the first characterization of ANP binding sites in different structures of the human kidney. Characterization of ANP binding revealed by Scatchard plot analysis a single class of high affinity binding sites in the glomeruli (K d 0.53±0.11 nM;B Max 74.4±17.86 fmol/mg protein), the vasculature (K d 0.18±0.014 nM;B Max 91.6±25.02 fmol/mg protein), and the medulla (K d 0.34±0.13 nM;B Max 106.0±30.61 fmol/mg protein). These sites may play a key role in the actions of the cardiac hormone in human kidney and in the ameliorating effects of ANP in the recovery from acute renal failure.

Notes: Summary Three hundred forty-eight outpatients without evidence of renal disease were examined by ultrasound. Their ages ranged from 18 to 83 years. Unexpected renal cysts of more than 1 cm were found in 47 patients (13.5%). No cysts were demonstrated in patients less than 23 years old; thereafter the number of patients with cysts increased significantly with age. The cyst diameter also tended to increase with age, but the correlation with age was not significant. There was no statistical difference of cyst occurrence between the right and left kidney, or between males and females. The upper portion of the kidney was most often affected in the equally divided three portions along the long axis. These results confirm that the development of simple renal cysts is age-related.

Notes: Summary The role of the kidney tubules in the renal formation of erythropoietin is incompletely understood. Therefore, the capability to produce erythropoietin in response to hypoxia was studied in rats with tubular lesions. Nephron damage was induced in two different ways. First, rats were treated with the nephrotoxic aminoglycoside gentamicin (67.5 mg/kg and day) for 14 days. The animals were then subjected to simulated altitude (6,800 m) for 6 h. The resulting plasma erythropoietin concentration was significantly lower (0.5 IU/ml) than in saline treated control rats exposed to hypoxia (1.0 IU/ml). Second, unilateral hydronephrosis was induced by ureteral ligation. The contralateral kidney was removed immediately before the animals were exposed to siulated altitude for 6 h. The plasma erythropoietin concentration in the ureterligated rats did not increase above the value (0.3 IU/ml) in hypoxia exposed anephric rats. These results indicate that the production of erythropoietin is reduced following tubular injury. Tubule cells may diretly produce the hormone or interfere with the O2-sensing mechanisms controlling its synthesis. The latter hypothesis would seem to be supported by our failure to demonstrate in vitro erythropoietin production by the two established kidney tubule cell lines, LLC-PK1 and PK-15.

Notes: Summary Kidney growth after induction of experimental diabetes in rats was compared to compensatory renal growth in response to unilateral nephrectomy. After 4 days of diabetes, kidney weight had increased from 816±21 mg (SEM) to 940±42 mg (15%). In insulin-treated diabetic rats kidney weight was unchanged at the end of the study, namely 828±15 mg. In unilaterally nephrectomised rats kidney weight increased from 840±20 mg (SEM) to 1050±60 mg during 4 days (24%). We observed increased kidney content of somatomedin C in both diabetic and uninephrectomised rats. In untreated diabetic rats it was maximal after 48 h, with an increase of 77% (3469±312 ng/g (SEM) versus 1961±173 ng/g). After 4 days the somatomedin C content had returned to initial levels. In insulin-treated rats somatomedin C content did not increase during the observation period. The somatomedin C content of the remaining kidney after unilateral nephrectomy was maximal after 24 h with an increase of 58% (from 1340±203 ng/g (SEM) to 2122±214 ng/g). The somatomedin C content returned to normal at day 4. Serum somatomedin C declined insignificantly in diabetic animals during the experimental period, but a significant decrease (p〈0.02) was found in uninephrectomised rats. This study demonstrates that kidney somatomedin C peaks during the first or second day after uninephrectomy or induction of diabetes, respectively, and that insulin treatment sufficient to prevent kidney growth abolishes the increase. These similar rapid initial hypertrophies/hyperplasies may thus be dependent on local somatomedin C formation.

Notes: Summary Urinary excretion of beta-hexosaminidase (NAG = N-acetyl-beta-glucosaminidase) and albumin was examined in 41 chlor-alkali workers exposed to inorganic mercury and 41 age-matched controls. Either U-HG or B-Hg levels for these workers were available dating from the 1960s to the present. Increased U-NAG was seen in workers with a U-Hg today of more than 4μg/mmol creat (about 50μg/l; 35 μg/g creat). Multiple linear regression analysis showed that U-NAG was correlated to U-Hg and integrated dose but not to the present B-Hg level. No albuminuria (detection limit 12.5 mg/1) was found in any of the subjects. In a longitudinal study, no decrease in UNAG levels was seen in 15 chlor-alkali workers after their vacation (x = 20 d). In five workers followed for ten months after a short exposure period, no definite time trend could be seen. The results show that there is a slight effect on renal tubules even at rather low levels of exposure to mercury vapour. The clinical significance of the enzymuria levels found here is, however, debatable.

Notes: Abstract The proximal tubules of newborn and adult animals reabsorb a similar fraction of the filtered load of Na+ and H2O (65%–70%). In tubules from adult animals, transcellular, active Na+ reabsorption accounts for one-third of the total, while two-thirds occur passively through the paracellular pathway, driven by hydrostatic and oncotic forces (one-third) and by cell-generated effective osmotic and ionic gradients (one-third). Since two-thirds of the Na+ is reabsorbed passively and does not require energy, the mature proximal tubule has a high Na+/O2 molar ratio (48 Eq of Na+/mol of O2). Measurements of ouabain-sensitive oxygen consumption in suspensions of proximal tubules indicate that in newborn, aerobic metabolism can support about 50% of the net Na+ transport rate compared with the 33% in tubules from adult animals. Independent confirmation of the direct and proportional relationship between active Na+ transport and ouabain-sensitive O2 consumption exists for the adult but not for the newborn. However, measurements of epithelial conductances and of transepithelial hydrostatic and oncotic pressure differences indicate that passive paracellular fluxes can account for the remaining 50% of the proximal Na+ reabsorption in newborn. The high permeability of the proximal tubules of newborn animals to small molecular weight solutes suggests that cell-generated osmotic and ionic transepithelial gradients are minimal in the tubules of newborn animals. Yet in the newborn, the osmolality of the end proximal tubule fluid was found to exceed that in plasma. This indicates that osmotic gradients due to differences in reflection coefficients for preferentially reabsorbed solutes and Cl− do exist across the proximal tubules of the newborn and suggests that these gradients may contribute to Na+ and H2O reabsorption. If this is indeed the case, then the contribution of active and of hydrostatic and oncotic pressure-driven flows to the overall reabsorption of Na+ and fluid has been overestimated. Resolution of this discrepancy requires measurements of the reflection coefficients for HCO 3 − and Cl− in the proximal tubule of the newborn. The metabolic processes by which energy is supplied to renal proximal cells during development are also incompletely characterized. There is evidence that maturation of aerobic metabolism, Krebs cycle enzymes activity, and of the mitochondrial membrane surface area precede the development of net reabsorptive transport (Na+, H2O, HCO3, glucose). By contrast, maturation of Na+−K+-ATPase activity at the basolateral cell membrane follows that in reabsorptive transport and does not limit its development. The extent to which age-related changes in reabsorptive fluxes are due to the development of luminal membrane transport systems, to the decrease in paracellular permeability, or both remains to be determined. The high activity of enzymes in the hexosemonophosphate pathway and the high NADH/NAD ratio present during the first few weeks of extrauterine life poise the proximal tubules for high rates of biosynthesis of membrane lipids, glycoproteins, nucleic acids, and transporter proteins necessary for final differentiation.

Notes: Abstract The developmental changes in epidermal growth factor (EGF) have been studied in tissue homogenates, kidney slices, and microdissected nephron segments of the mouse. Immunoreactive EGF concentration per milligram of protein increased in the kidney by about 20-fold from 1 week to 3 weeks of life, reaching the highest levels between 5 and 7 weeks, and decreasing by 10 weeks of life. The time course of the changes was different from those of submaxillary and urinary EGF. Above 7 weeks of age, kidney EGF was higher in female than in male mice. Among various zones of the kidney (outer cortex, inner cortex, outer medulla I, II and papilla), the outer medulla I and II contained the highest quantities of EGF per gram of wet tissue. The highest EGF content per millimeter length was observed in the medullary and cortical thick ascending limbs of Henle's loop. The amounts exceeded by about 4.5-fold those found in glomeruli and in proximal convoluted and proximal straight tubules, and by about 3-fold those present in distal and collecting tubules. Unilateral nephrectomy resulted in no significant changes in EGF levels in the contralateral kidney. The results suggest that the ontogeny of kidney EGF is different from that of the EGF found in the submaxillary gland, and that there is nephron heterogeneity in EGF content.

Notes: Abstract These studies were designed to characterize dopamine receptor density and affinity in kidneys removed from sheep of varying ages (fetal, newborn, and adult) using radioligand binding methods. Three different radioligands were used: the specific dopamine-1 antagonist3H-SCH 23390, the dopamine-1/dopamine-2 antagonist3H-haloperidol, and the dopamine-2 antagonist3H-spiroperidol. The specific binding of3H-haloperidol and3H-spiroperidol was saturable with time and ligand concentration, being indicative of dopamine receptors. The specific binding of the dopamine-1 selective radioligand3H-SCH 23390 was also saturable with time but displayed several points of saturation with increasing ligand concentration. The specific binding of3H-haloperidol, which had a low affinity and is indicative of dopamine-1 receptors, showed no age-related changes in maximum receptor density or affinity. On the other hand, the maximum receptor density of dopamine-2 receptors measured by3H-spiroperidol decreased with age. The observations that renal dopamine-1 receptor density or affinity do not change with maturation are in agreement with our pervious studies that showed no age-related changes in dopamine-receptor-mediated renal vasodilatation in sheep. The significance of the decrease in renal dopamine-2 receptor density with age remains to be determined.

Notes: Abstract The influence of chronic adriamycin treatment on cellular defence mechanisms against free radicals has been determined in rats. To that end, the changes in vitamin E content, activity of superoxide dismutase, catalase and factors of the glutathione system were measured in heart, kidneys and liver after 24 and 52 days of treatment. Moreover, damage was assessed by measuring the activity of NADPH- and NADH-cytochrome c reductase. The results concerning the components of the oxidative defence systems in male rats showed reductions in the activity of superoxide dismutase and catalase in renal tissue and in factors of the glutathione system in liver tissue. In cardiac tissue an increased activity of catalase and elevated content of total glutathione were found. Vitamin E content was increased in liver and to a lesser extent, in kidneys. The activity of Se-dependent glutathione peroxidase sharply decreased only in liver. Major differences between male and female rats were not observed in renal and cardiac tissue, as far as protective factors were concerned. However, a decrease in catalase activity was detectable earlier in male kidneys. The protective factors in liver of female rats were far less susceptible to in vivo treatment with adriamycin, as compared to liver of male rats. Decreased activity of the cytochrome reductases was found in liver of male rats. In male renal tissue only cytochrome c reductase activity was significantly reduced. Male cardiac tissue showed no signs of biochemical damage, although from histological examination in a parallel study [J Natl Cancer Inst 76: 299–307 (1986)] lesions were evident. In female rats no damage was found in liver, kidneys and heart.

Notes: Abstract A boy was first seen at the age of 1 year on account of congestive cardiomyopathy. Growth and development had been normal. Total plasma carnitine was extremely low (1.8 μmol/l; normal range: 25–64 μmol/l). No hypoglycaemia, lactic acidaemia or dicarboxylic aciduria were found. Other laboratory findings were unremarkable except for a slight deficiency in iron, vitamin D and vitamin E. Total muscle carnitine was 1.5% of normal; however, no signs or symptoms of myopathy could be detected. After carnitine loading, liver carnitine increased to 24% of normal. Isolated muscle mitochondria showed decreased oxidative capacity with all substrates tested. Stimulation of O2 uptake by adenosine diphosphate (ADP) was decreased. After loading with both intravenous and oral carnitine, there was a rise in plasma carnitine and a rapid loss in the urine and the faeces. These findings suggest a defect in the brush border carnitine transport system of the kidneys and of the small intestine. Renal clearance of carnitine was abnormally high. Therapy with 1 g oral l-carnitine/kg per day was instituted without any problems and the cardiac disease resolved within 3 months. The parents and the patient's five sibs also had low plasma carnitine but displayed no cardiomyopathy.

Notes: Summary Like other lipid-soluble xenobiotics, clofibrate (ethyl-2-(4-chlorophenoxy)-2-methylpropanoate) increased the level of microsomal cytochrome P-450 in liver and decreased the utilization of 14C-orotic acid for the synthesis of hepatic cytidine nucleotides. This phenomenon was associated with the increased (a) uptake of 14C-cytidine, (b) total content of cytidine components of the acid-soluble extract and (c) utilization of this nucleoside for the synthesis of RNA. No changes were observed in uridine components. Clofibrate also increased the level of cytochrome P-450 in kidney microsomes; the degree of induction was almost the same as in the liver. The variations of renal pyrimidine metabolism after administration of the drug were analogous to those observed in the liver.

Notes: Abstract Isolated guinea-pig kidney cortex tubules were incubated in Krebs-Henseleit buffer containing NaH14CO3 (25 mM) andl-alanine (5 mM). A high rate of alanine metabolism was found to be accompanied by a high rate of both14CO2 fixation and glutamine synthesis. The fixation of14CO2 was virtually abolished in the presence of oxalate, a known inhibitor of pyruvate carboxylase, indicating that, in guinea-pig renal cortex, this enzyme is responsible for the synthesis of oxaloacetate in the conversion of alanine into glutamine. More than 90% of the label fixed was found in carbon 1 mainly of glutamine and to a lesser extent of glutamate. In the presence of alanine+NaH14CO3+MSO, an inhibitor of glutamine synthetase, most of the14CO2 fixed by pyruvate carboxylase was subsequently released and carbon 1 of glutamate was the only site of labelling. In the presence of alanine+NaH14CO3, the fact that not all the glutamine found was labelled in carbon 1 could be explained by glutamine synthesis from endogenous substrates as well as by glutamine synthesis from alanine after prior equilibration of [4-14C]-oxaloacetate with fumarate; that such equilibration occurred was demonstrated by the observation that [1-14C]-glutamine and [1-14C]-glutamate were synthesized from [1-14C]-alanine.

Notes: Abstract Measurements of the water osmotic permeabilities of apical and basolateral membranes of PST cells and of the transepithelial permeability have been carried out using a very fast method with high temporal and spatial resolution. At 25°C the values obtained are: 80.8±11.9×10−4 cm3/s osmol cm2 of apical (luminal) surface area and 90.1 ±13.0×10−4 cm3/s osmol cm2 of basement membrane area (no membrane invaginations taken in account). These values are higher than previously published values due to the use of a faster and more accurate volume measuring and recording system. The transepithelial water osmotic permeability at 25°C is 77±11 in units of 10−4 cm3/s osmol cm2 basement membrane area. The transcellular water osmotic permeability is 32±7 (same units), leaving a paracellular contribution of 45±10 (same units). In the presence of 2.5 mM parachloromercuribenzenesulfonate (pCMBS) the apical permeability is reduced with an incubation of 10–15 min to 23% of its control value and the basolateral permeability to 8% of its control value (after 25 min) but the transepithelial permeability is only reduced to about 1/2 of the control value. This leaves a transcellular permeability of 6×10−4 cm3/s osmol cm2 of basement membrane area and a paracellular contribution of 33±6 (same units). These results indicate a significant contribution of the paracellular pathway to the transepithelial water osmotic permeabilities in PST.

Notes: Abstract It is generally assumed that the O2 supply to the kidneys is the major determinant of the synthesis of erythropoietin (Ep). In the present study, the O2 supply of the kidneys of rats was lowered by the reduction of renal blood flow (rbf). Plasma Ep was determined after about 18 h of bilateral application of Goldblatt clips with graded inner diameters. The results were compared to findings in anemic rats, in which the systemic O2 supply was lowered by exchange transfusion of blood with plasma. We found a linear correlation between Ep levels in plasma and the degree of reduction of rbf. However, there was an exponential relationship between Ep levels and the concentration of hemoglobin in blood. In addition, the elevation of plasma Ep was only moderate, when rbf was reduced (maximum 0.07 IU Ep/ml plasma). The increase in Ep concentration was much more pronounced in anemia (up to about 7 IU Ep/ml plasma). From these results it may be concluded that decreasing oxygen supply to the kidney through reduction in renal blood flow (ischemic hypoxia) is less effective in increasing erythropoictin production than reducing the hemoglobin concentration (anemic hypoxia). The possibility must be considered that the increase in renal production of erythropoietin due to anemic hypoxia is triggered by one or more extrarenal signals.

Notes: Abstract Transplantation of kidneys bearing HLA antigens to which recipients have previously been exposed is generally avoided, and such prudence is a well-documented means of preventing early graft loss. Prior exposure and subsequent reactions can, however, take a wide variety of forms, and blanket avoidance may prevent many deserving patients from being transplanted. In our region, operating through a single tissue-typing laboratory, we follow a consistent policy of allowing retransplantation with kidneys bearing previous mismatches, provided no relevant antibody response has been detected. Twenty-one of 34 such transplants remain functioning at time periods ranging from 7 months to 7 years. Four were lost due to rejection within the 1st month, and the remaining 9 functioned for periods ranging from 2 months to 8 years. Three were lost for reasons other than rejection. Our antibody screening policy and our criteria for a negative crossmatch results in the exclusion of two-thirds of all repeat mismatch transplantations. The results indicate that in the remaining third, transplantation can be performed across a repeat mismatch with excellent long-term results, provided our defined crossmatch policy is adhered to strictly.

Notes: Summary In an effort to investigate the functional relationship between cell-specific work and intracellular degradative processes, the effect of furosemide on cellular autophagy was investigated in two different portions of the nephron, namely, the thick ascending limb of Henle's loop (TAL), which is a main target of this drug, and the proximal convoluted tubule (PCT) as a reference structure. Eight male adult rats were treated with furosemide (60 mg/kg body weight, s.c.). Eight control animals received physiological saline. 1 to 4 h after the injections the animals were killed by perfusion fixation. Small specimens of kidney tissue from the inner stripe of the outer medulla and from the outer cortex were processed for electron microscopy; they were investigated morphometrically for volume fraction and numerical density of autophagic vacuoles (AVs). A significant increase of both parameters (volume fraction: 0.42 × 10-4 to 1.09 × 10-4; numerical density: 4.2 × 105/mm3 to 15.5 × 105/mm3) was seen under the influence of furosemide in TAL cells, whereas PCT cells did not show a significant increase in volume fraction or any increase in numerical density of AVs. These data suggest that the functional unloading of TAL, via blocking of the Na+- 2Cl- — K+ co-transport by furosemide, results in adaptative “structural unloading”, i.e., an increased sequestration of cytoplasmic components into AVs, within a short-time interval.

Notes: Summary Previous immunohistochemical data have shown that the 44-kDal bone phosphoprotein (44K BPP, also called sialoprotein I or oestopontin) recently isolated in our laboratory was synthesized by osteoblasts and osteocytes and was expressed early during differentiation of boneforming cells. We report here the presence of 44K BPP antigenicity at certain ectopic sites, namely, the proximal-convoluted tubule of the kidney, neurons, sensory and secretory cells in the internal ear. To insure specificity and reproducibility, different immunohistochemical methods were used and affinity-purified antibodies against two separate preparations of pure 44K BPP were tested. In the cells of the proximal-convoluted tubule, 44K BPP immunoreactivity was observed within apical endocytotic vacuoles and within lysosomes. This staining thus correlates with the degradation of the 44K BPP epitope which we previously demonstrated to occur in serum. On the other hand, in the neurons of the acoustic ganglion and the sensory cells of the macula, 44K BPP immunoreactivity was associated with the Golgi apparatus indicating synthesis and secretion by these cells. The finding that the 44K BPP (or a structurally related molecule) is synthesized by neurons and neuroepithelial cells deserves further investigation with respect to a possible embryologie relationship between neuroectodermal cells and the precursors of some bone forming-cells of the skull.

Notes: Summary Two cytochemical techniques were used at the ultrastructural level to study the distribution of specific axon types to different intrarenal structures in the dog. Using the chromaffin reaction to distinguish catecholaminergic fibres from other axon populations, it was found that the renal cortex of the dog is supplied only by catecholaminergic nerves. Immunostaining for tyrosine hydroxylase (TH) labelled all of the intracortical nerves, and 20% to 25% of these profiles also contained dopa decarboxylase (DDC)-immunoreactivity, indicating they were dopaminergic rather than noradrenergic. Both DDC-positive and DDC-negative axons were seen in close association (∼80 nm) with blood vessels and juxtaglomerular cells as well as tubular epithelial cells. The distribution of TH- and DDC-immunoreactive nerves in the renal cortex is compatible with existing functional evidence indicating that both dopaminergic and noradrenergic nerves are involved in the regulation of renal blood flow, tubular reabsorption and renin release.

Notes: Summary The mesangial matrix of the rat glomerulus was studied by transmission electron microscopy in specimens preserved by a modified technique, which avoids osmium tetroxide but uses tannic acid as a contrasting agent. It can be demonstrated that microfibrils are a major component of the normal glomerular mesangial matrix. They are non-branching tubular structures with a hollow centre, an undefined length and a thickness of ∼15 nm. Microfibrils make up a dense fibrillar network interconnecting mesangial cells and glomerular basement membrane.

Notes: Summary A stable epithelial cell line has been established from the kidneys of a normal Sprague-Dawley rat. This line, termed RK-L, has a high proliferative capacity (minimal doubling time 12.3 h) and can be grown in medium containing 1% fetal bovine serum. Thus far, the line has been carried through more than 60 serial passages. The RK-L cells were found to display similarities with kidney tubule cells. Using light microscopy, confluent cultures were seen as pavement-like monolayers forming domes, which are thought to result from transepithelial fluid transport. Electron microscopy revealed polarized cells that had microvilli on the apical surface, junction complexes in the apical part of the lateral cell membrane, and a basal lamina-like layer. Pinocytotic activity was indicated by infoldings of the apical plasma membrane and the formation of vesicles. The RK-L line should prove useful for investigations of kidney tubule transport mechanisms.

Notes: Summary The secretory granules of marine epithelioid cells take up and probably degrade mitochondria; they thus appear to have macroautophagic properties. As renin granules also have other properties uncommon for secretory granules, they are suggested to fulfill functions in these cells otherwise reserved for lysosomes.

Notes: Summary Changes in blood composition, renal function, aldosterone and antidiuretic hormone (ADH) concentrations were investigated in 10 untrained male subjects when swimming (60 min at a heart rate of about 155 beats·min−1, water temperature 28° C) and during the subsequent 3 h in a sitting position. Many specific effects of either exercise or immersion were abolished or attenuated; no significant changes in plasma aldosterone, [ADH], [K+], [Cl−], or of urinary volume, glomerular filtration rate, free water or osmolar clearance were observed. The urine was diluted resulting in lowered [Na+]. In blood some quantities which are only slightly influenced by immersion increased during swimming ([Na+], [Lac−], [H+], osmolality, [creatinine]). Exercise induced plasma volume loss, calculated from increasing [Hb], was small (110 ml), probably because interstitial fluid enters the vascular space during the initial phase of immersion. One might anticipate that the training effects on fluid and electrolyte metabolism and circulation are different when swimming and when performing endurance sports on land.

Notes: The aim of this presentation is to draw attention to the problems inherent in evaluating the ultrastructure of percutaneous renal biopsies and to discuss some of the special techniques which are useful in this area. It is important to realize that the ultrastructure as it appears in this kind of material does not necessarily reflect conditions in vivo. Comparison with suitable reference material may, however, permit reliable conclusions in terms of pathological diagnosis and pathogenesis. It is advocated that purely qualitative methods, which until now have predominated in ultrastructure work with renal biopsies, be replaced by morphometry and semiquantitative methods when it is possible and practical to do so in any research situation.

Notes: The glomerular (visceral) layer of Bowman's capsule is comprised of a unique population of cells which have been termed “podocytes.:” Arising from these cells are large major processes and numerous smaller foot processes which completely surround underlying glomerular capillary loops. Podocyte foot processes interdigitate with each other and are separated by spaces (filtration slits) which are designed to facilitate flow of a large amount of filtrate across the glomerular wall. Podocytes exhibit dramatic morphological changes in response to the nephrotic syndrome and some forms of acute renal failure and may play an important role in the pathophysiology of these conditions. In vitro and in vivo studies have shown that a reduction in the sialic acid component of a thick anionic surface coat plays a major role in the morphological changes that these cells exhibit in the nephrotic syndrome. Also, it has been shown that filamentous actin concentrated mainly within podocyte foot processes are the contractile elements responsible for altering the shapes of these processes. There is evidence to suggest that by altering the shapes of their foot processes, podocytes in the normal kidney are able to alter the number of fully patent filtration slits and thereby actively regulate the rate of solute efflux across the glomerular wall. In vitro and in vivo studies have indicated that cytoplasmic microtubules are probably not involved in alterations of the podocyte foot processes but do appear important in maintaining the morphological integrity of podocyte cell bodies and their major processes. In the present paper, the morphological changes which glomerular podocytes exhibit in response to the nephrotic syndrome, various forms of acute renal failure, and during in vitro incubation are discussed along with studies of the possible roles of cytoplasmic microtubules, microtubules, and the glomerular anionic surface coat in these changes.

Notes: Summary Samples from renal and thyroid oncocytomas were studied with antibodies against intermediate filament proteins, nephron site specific antigens and nephron segment specific lectins to gather information on the immunohistological and carbohydrate histochemical features of these tumours. The results show a surprising failure of most antibodies and lectins used to react with the oncocytomas, although readily staining the surrounding normal tissue areas. No immunohistological evidence for derivation of oncocytomas from proximal tubular epithelial cells could thus be found. Instead,Triticum vulgaris (wheat germ agglutinin; WGA) andConcanavalin A (ConA) lectins were seen to stain the oncocytes specifically, suggesting that these lectins are useful to further characterize oncocytomas.

Notes: Summary The purpose of the work was to develop an in vitro model for the study of human kidney development. Human metanephric explants from foetuses 10–18 weeks of gestational age were cultured in serum-free Leibovitz L-15 medium without hormones. Under the current minimal conditions for growth, the system permitted to maintain the renal tissues in culture for periods up to 9 days, although no evident sign of morphological differentiation was observed. However, during the studied period the overall architecture of the explants was preserved as well as the ultrastructural features of cytoplasmic organelles. The incorporation of 3H-thymidine and 3H-leucine indicated that DNA and protein synthesis was maintained or increased. Glycoprotein synthesis evaluated by 3H-glucosamine incorporation and radioautography continued in mesangium as well as in glomerular and tubular basement membranes. Alkaline phosphatase, γ-glutamyltranspeptidase (brush border) and catalase (peroxisomes) activities remained histochemically active. The proposed organ culture system appears as a reliable and promising model that will provide basic data on the morphology and functional characteristics of the developing kidney. Since it is achieved in a completely controlled environment, it will permit to study the role of growth factors and hormones in proliferation and differentiation of the cell populations during development of the human foetal kidney.

Notes: Abstract This study presents the result of 12–21 years' follow-up in a group of children with neonatal urinary tract infection (onset within 1 month after birth) in whom early renal growth retardation was noted without concomitant classical renal scarring. In all cases the neonatal infection was diagnosed and treated within a few days of onset and the patients were closely supervised thereafter. Renal length, parenchymal thickness and area were measured at urography. At first follow-up (22 children, mean age 4.1 years) a significant reduction of renal parenchymal thickness was noted. Long-term follow-up (18 patients, mean age 17 years) demonstrated a normalization of renal size in the entire group, although less complete in the subgroup with reflux. There were two major findings in the present study. Firstly, renal growth retardation was seen after neonatal infection, both with and without reflux. Secondly, normalization of renal size in previously small kidneys was demonstrated, suggesting that growth retardation can be a reversible phenomenon. The tendency for such normalization was slightly more marked in children without reflux. Reduction of parenchymal thickness without calyceal deformity, therefore, does not necessarily mean irreversible damage, and differentiation between permanent scarring and temporary growth retardation can thus only be made at later follow-up, possibly not until after puberty. The demonstration of renal growth retardation in spite of early diagnosis and treatment emphasizes the great vulnerability of the kidney in the newborn.

Notes: Abstract We briefly review what appear to be the most important elements responsible for renal cell injury during and after oxygen deprivation. Recent studies in numerous laboratories have vastly improved our understanding of the changes in cell function that occur during ischemia and yet, the underlying mechanisms by which tubule damage and cell death occur remain elusive. We attempt to separate the effects that occur during ischemia or anoxia from those occurring during reperfusion (reoxygenation). These are not always separable, especially because it appears that ischemia initiates a series of complex events that may only become manifested during reperfusion. Ischemia-induced renal dysfunctions are clearly multifactorial events that will require major efforts to unravel.

Notes: Abstract An attempt has been made to identify the subcellular localization of renal corticosteroid metabolism. Subcellular fractions were prepared by differential centrifugation, identified by marker enzymes and incubated under different conditions with corticosterone (B). The NADP+/NADPH dependent metabolism of B could be localized in the nuclear and microsomal fraction. The most prominent metabolite was 11-dehydro-B, which is formed by 11β-hydroxysteroid dehydrogenase (EC 1.1.1.146). Enzyme kinetic studies of this enzyme with B as substrate revealed apparentK m-values in the range of 10−7 M for both the nuclear and microsomal fraction.

Notes: Abstract Previous studies in rat kidneys have demonstrated that oscillations in the proximal intratubular pressure are a prominent feature of the tubulo-glomerular feedback mechanism (TGF) operating during free flow conditions. The purpose of the present study was to investigate whether a subpopulation of synchronized, interacting nephrons could be detected. In group A nephrons, i.e., nephrons with a high probability of having their afferent arterioles arising from the same interlobular artery, 29 out of 33 pairs of nephrons were found to show synchronized pressure oscillations. In group B nephrons, not expected to have this common origin of their afferent arterioles, only 1 out of 23 pairs was found to be synchronized. The standard deviation of the frequency differences was 0.063 cycles per minute in group A nephron pairs and 0.202 cycles per minute in group B pairs (p〈0.05), showing the greater homogeneity in frequency in group A. Furthermore, nephrons having synchronized pressure oscillations were found to interact with each other. Thus, perturbation of the proximal tubular pressure oscillations in one nephron by loop microperfusion affected the amplitude of the pressure oscillations in the non-perfused nephron; and reactivation of pressure oscillations in one nephron was followed by reactivation of oscillations in the non-perfused nephron. Thus, the present results show that there exists a well defined subpopulation of nephrons, in which the TGF-mediated proximal pressure oscillations are synchronized. This synchronization is a result of interaction between the different nephrons. It is suggested that the interaction is a consequence of “cross-talk” between the TGF signals from the different nephrons concerned, transmitted along the afferent arterioles, and probably also along a part of the interlobular artery.

Notes: Abstract A method for automated image capture and analysis of shrinking drop sequences is described. The procedure can be managed by a single operator and allows estimates of proximal tubule volume flux to be calculated during the experiment. Speed of analysis is increased considerably (mean time 1.5 min per sequence) compared with previous methods. The potential exists for measurement of droplets in tubules that follow a tortuous path in the horizontal plane and further increases in capture and analysis rate would allow estimation of volume flux under non-steady state conditions. Film processing is eliminated and the removal of operator errors, bias and fatigue associated with manual measurement, coupled with the greatly reduced time required for analysis of sequences makes the shrinking drop method much more reliable and attractive.

Notes: Abstract Drug transport in intestine, liver and kidney is similar, because in each case transport occurs across a barrier of epithelial cells. However, the physiological conditions differ in each organ: intestinal drug absorption is largely influenced by physicochemical conditions in the intestinal lumen; actual transport across the epithelial barrier occurs mainly by diffusion; carrier-mediated transport plays a subordinate role. In contrast, hepatic uptake is mediated by specific carriers, which transport a wide variety of drugs into the liver cell and then release them either into bile, or back into the portal blood. It is unclear how many carrier systems are involved, how they are organized in the liver cell membrane, and to what extent their substrate specificities overlap. Renal secretion and reabsorption of drugs is mediated by highly active carrier systems for cations and anions. Their cooperative action results in either active reabsorption or active secretion of drugs.

Notes: Abstract A single dose of clofibrate (400 mg/kg), given to rats, increased the incorporation of (3H)thymidine into liver DNA, in a period of 20–30 h after administration. However, (3H)thymidine incorporation into hepatic DNA of rats treated repeatedly was identical to that of control animals. After the administration of a single dose of clofibrate a small increase in (3H)thymidine incorporation also occurred in kidney DNA; repeated doses, however, resulted in a marked suppression of labeling.

Notes: Summary Attempts by early workers to induce liver tumours by the local implantation of carcinogens had by and large not been successful, so that the liver came to be viewed as being “resistant” to tumourigenesis by this means. A review of these early studies showed not only that fibrosarcomas could be easily induced by the local application of 3-methylcholanthrene (3-M.C.), but that there were also reasons why the apparently low susceptibility of the liver to the localised induction of hepatocellular tumours should not be accepted as established dogma. In an attempt to re-investigate this problem pellets made of chlolesterol (CHOL), anthracene (ANT), α-naphthylisothiocyanate (ANIT), 3-M.C. or 4-dimethylaminoazobenzene (DAB) were implanted into the livers of male litter-mate weanling rats. The evolution of the response was studied by histological examination of the implantation site at varying intervals. In each instance the liver responded with the formation of a firm, complete connective tissue capsule which, however, did not prevent the gradual degradation of the implants. No tumours or other significant changes were observed with the control implants of CHOL or ANT. ANIT, known to damage biliary ducts, elicited what appeared to be an intense serous exudation which was separated from the adjacent parenchyma by a shell-like deposition of calcium in the connective tissue capsule. No significant biliary changes were observed, however, and no tumours were produced. Attention should be drawn to this reproducible, regularly occurring, in vivo model of extra-osseous calcification. The 3-M.C. induced a high incidence of large solitary bosselated tumours associated with the carcinogenic pellet which was found embedded in the tumour mass. The architectural arrangement and bizzare cytological appearance of the tumours led to the currently widely used diagnosis of malignant fibrous histiocytoma (M. F. H.) rather than the fibrosarcoma or rhabdomyosarcoma of the early workers. Some tumours produced large numbers of implantation metastases in the peritoneal cavity, but no distant metastases were observed in this series. Of particular interest is the fact that it was not possible to determine the site of origin of these tumours despite histological sampling at intervals of the site of implantation of the pellets. In contrast to these pleomorphic, clearly mesenchymal tumours reliably produced by 3-M.C., the implantation of pellets of DAB produced fewer tumours which were classified as large, singly occurring hepatocellular carcinomas (H. C. C.). They did not differ in their histological appearance from the description of tumours induced by feeding the carcinogen. Metastases occurred again by implantation in the abdominal cavity. It appears that this is the first experiment in which the reproducible induction of localised H. C. C.s in the liver of the rat has been reported, the only previously reported instance of the induction of H. C. C. by this means having been described some considerable time ago in mice prone to the occurrence of “sponanteous” hepatocellular tumours. This report was disregarded for that reason. The rather low numbers of H. C. C.s induced by DAB implants in the experiments reported here, and their long latency period, suggests a need for further experimental manipulation. None of the usually described associated or precursor phenomena—oval cell proliferation, fasting-resistant glycogen accumulation, nodule formation—were seen either in the parenchyma immediately adjacent to the pellet or in more distant areas. The advantages of this model for further experimentation, and its position in the light of current views of hepatocarcinogenesis, are indicated, while some unsolved problems are underlined. The response of the kidney differed to some extent from that seen in the liver. The implanted pellets of DAB were encapsulated and grdually degraded, but no tumours were induced either in the kidney or, at a distance, in the liver. With pellets of 3-M. C., however, large hydronephrotic cysts with squamous cell metaplasia of the transitional pelvic epithelium progressing to invasive and locally metastasizing squamous cell carcinoma were produced in the kidney of some rats, whereas in others M. F. H.s were the outcome; one of the rats also presented with a mixed tumour. The similarity of the appearance of the 3-M. C.-induced tumours in liver and kidney suggests that the implantation of pellets of 3-M. C. is a reliable tool for the experimental study of M. F. H.s in internal organs.

Notes: Summary This report describes the immunolocalization of three monoclonal antibodies along the collecting duct system in rabbit kidney. The antibodies were raised against antigens derived from a membrane fraction of homogenized papillary tissue. Western Blot analysis demonstrated that each of the antibodies recognized a single band of about 190000 (PCD1), 210000 (PCD2) and 50000 (PCD3) daltons. In renal tissue, the antibodies bound specifically to the epithelia of the connecting tubule (CNT), the collecting duct (CD) and the papillary surface epithelium. Differences in the binding patterns of the antisera were limited to the cortex. pCD1 labeled only a few scattered cells in the CNT, and exhibited a heterogeneous binding along the cortical collecting duct (CCD). PCD2 and PCD3 binding patterns were similar. In the CNT, these antibodies bound to the intercalated cells (IC-cells) but not to the CNT-cells proper. In the CCD, both IC-cells and principal cells were labeled. The binding to the medullary collecting duct by all three antisera was identical. The ureter was labeled only by PCD2 and PCD3, and none of the antisera bound to the bladder epithelium. The antibody binding patterns provide information concerning tubular axial heterogeneity and embryogenetic aspects of the CNT and the CCD. These antibodies may be used as differentiation markers in studies of the developing kidney and of renal tissue culture systems.

Notes: Summary The cells of the kidney proximal segment of the migrating arctic lamprey, Lampetra japonica, contain particles of the same size, electron-density and intracellular location as particles identified by others as very low-density lipoproteins (VLDL) in the liver and intestine of teleost fishes and lampreys. These particles are synthesized within the cisternae of the smooth endoplasmic reticulum and elements of the Golgi complex. They are transferred to the lateral intercellular space and lamina propria by way of the Golgi vesicles and an intracellular channel system. Some particles are discharged into the lumina of the sinusoidal capillaries of the lamina propria. Although the physiological role of lipoprotein secretion in the renal proximal segment cells is unknown, the present observations provide morphological evidence that the kidney of the arctic lampreys synthesizes lipoproteins and releases them into the circulation at the time when they are undertaking their anadromous migration.

Notes: Summary Rats were given a lithium-containing diet (40 mmol/kg) to Study the effect of lithium on the structure of collecting ducts from the inner stripe of the outer medulla. The results show that there is a significant increase in the volume density of collecting ducts already after one week on this diet. The volume density of both intercalated and principal cells increases, whereas the volume density of mitochondria in the cytoplasm increases in the intercalated cells only. The increased volume of both principal and intercalated cells seems to be part of a general hyperplasia and hyperactivity of the collecting duct, which may in some way be related to the effects of lithium on vasopressinmediated water transport. The specific changes in the intercalated cells may be a consequence of the effects of lithium on distal nephron potassium and hydrogen ion transport in the distal nephron.

Notes: Summary This investigation provides histochemical evidence for lysosomal storage of sulfated glycosaminoglycans (GAGs) in the interstitial cells of the renal cortex and in macrophage-like cells of the renal medullary zones of rats chronically treated with the drug tilorone. This compound is known to interfere with lysosomal degradation of sulfated GAGs; therefore cells that develop GAG-storage can be assumed to be involved in the turnover of GAGs. In view of this consideration, the most remarkable and still unexplained finding was that the intrinsic interstitial cells in the papilla, which is known to be particularly rich in sulfated GAGs, did not show the cytological symptoms of lysosomal GAG-storage. The present findings may stimulate further studies focused on the cellular sites of turnover of the sulfated GAGs present in the renal medullary interstitium.

Notes: Summary The spatial organization of endoplasmic reticulum (ER) was examined in all segments of rat nephron. Tissues were fixed with glutaraldehyde, impregnated “en bloc” with osmium tetroxide, prepared for and examined by standard (80–100 kV) and high voltage (1 mEV) transmission electron microscopy. In all proximal tubule cells, ER forms a continuous and extensive network of canaliculi and abundant fenestrated saccules which surround mitochondria and cytoplasmic bodies; the cage-like structure of the fenestrated saccules was most evident around the spherical mitochondria of the S3 segment. In the cells of the distal straight and convoluted tubules, the network consists mostly of canaliculi with rare non-fenestrated saccules. The ER network of canaliculi is particularly rich in intercalated cells, in contrast with its rudimentary appearance in the adjacent principal cells of the collecting tubule. In fact, in these cells there are few isolated ER cisternae and they are rarely impregnated. The nuclear envelope is well impregnated in most cells throughout the various segments. Segmental variations in ER organization and its relative abundance are most likely related to the well, established functional heterogeneity of the nephron segments. Moreover, the extensive and unique organization among mitochondria, ER and the basolateral membrane suggests that these three organelles function as a unit which is related to active electrolyte transport. In addition, because of its transepithelial organization, ER may well constitute a transcellular pathway for molecules.

Notes: Summary The nephrons of the freshwater turtles Pseudemys scripta elegans and Mauremys caspica consist of renal corpuscle, neck segment, proximal tubule, intermediate segment, distal tubule and collecting duct. The renal corpuscle has large and scarce capillaries with clear and dark fenestrated endothelial cells containing some rod-shaped bodies, a thin filtration barrier and a well-developed mesangium, the cells of which show secretory, phagocytic and contractile features, and in M. caspica a cilium. The podocytes with a well-developed Golgi apparatus seem to be active secretory cells. Numerous dense bodies similar to lysosomes, but not previously reported in vertebrates, are conspicuous in podocytes of M. caspica. The proximal tubule displays a well-developed brush border with long and densely-packed microvilli and no basal labyrinth; mitochondria are scattered throughout the cytoplasm. Several dense and clear vesicles related to the prominent endocytotic apparatus can be seen. Wavy filament bundles, not previously reported in vertebrate kidneys, can be observed in proximal tubule cells of M. caspica. Three regions can be distinguished in the well-developed intermediate segment as well as in the distal tubule; the latter has a few short microvilli or a smooth luminal surface and lateral interdigitated processes. The collecting duct, the cells of which contain numerous mucous droplets, is similar in both sexes; there is no sexual segment.

Notes: Summary A monoclonal antibody against an antigen (PCD2) derived from the rabbit renal papilla recognized principal and intercalated cells of the collecting duct system in the adult rabbit kidney. Intercalated cells were heterogeneous in the connecting tubule and the cortical collecting duct, where immunoreactive and unreactive cells were shown to coexist. In the outer medullary collecting duct, all intercalated cells exhibited PCD2-immunoreactivity. Connecting tubule cells proper were not recognized by the antibody, whereas all principal cells of the collecting duct revealed specific immunoreactivity. The immunocytochemical heterogeneity of the intercalated cells is discussed in terms of a functional heterogeneity. Cytologically, the immunogold labeling of principal and intercalated cells was shown to occur along the plasmalemma, in the intracellular membrane structures and along the Golgi transport route. This pattern suggests that the antigenic determinant, which is ubiquitous in both principal and reactive intercalated cells, belongs to a membrane protein.

Notes: Summary The medullary pyramid of renculi in kidneys of ringed seals (Phoca hispida) is enclosed by a basket composed of ribbons of stromal tissue continuous with the wall of the calyx. Branched smooth muscle cells with well-developed Golgi complexes and rough endoplasmic reticulum and only an incomplete external lamina are the principal cells in sites near the origin of the ribbons from the calycal wall. Deeper in the corticomedullary junctional region, smooth muscle is progressively replaced with stellate or spindle-shaped cells exhibiting structural characteristics intermediate between those of fibroblasts and smooth muscle fibers. These myofibroblast-like cells contain arrays of parallel microfilaments 6–8 nm thick with associated focal densities and subplasmalemmal dense plaques, caveolae, elongate, often deeply wrinkled nuclei, and well-developed Golgi complexes and rough endoplasmic reticulum. Material resembling external lamina is associated with parts of the surfaces of most myofibroblast-like cells and intermediate junctions are present. Fibroblasts lacking arrays of parallel microfilaments are a minority at any level in the stromal ribbons. Interstitial cells in the vicinity of the corticomedullary junction show similar myofibroblast-like characteristics. The smooth muscle and myofibroblast-like cells presumably assist expression of urine from the papilla and calyx, and possibly participate as pacemakers for the urinary tract.

Notes: Abstract Two methods of glomerular filtration rate estimation have been evaluated, based on the intravenous administration of 99mTc-DTPA and the measurement of renal time activity curves by means of a computer linked gamma camera. A single 20 min plasma sample was also required. These methods were designed to minimize the component of error arising from decay statistics. One method was based on using a constant fraction of the cardiac activity in lieu of a perirenal region of interest for the background correction, the other was based on deconvolution by a constrained least squares technique. The first method, based on modifying the background correction, led to poor results (residual standard deviation 18.9 ml/min when compared with the plasma clearance method). The second method, based on constrained least squares deconvolution, worked as well as previously reported methods (residual standard deviation 14.5 ml/min) and appears suitable for clinical use.

Notes: Abstract It is now known that cardiac atria play an important role in blood pressure and volume regulation. Mechanical distension of the atria results in the release of a potent diuretic and natriuretic agent or agents termed the atrial natriuretic factor (ANF). Several structurally related forms of ANF exist in man and it is thought that these represent precursory forms of a single optimally active molecule and/or the presence of more than one form of active ANF. The chemical structure of ANF between different mammalian species is similar. ANF receptors have been identified in kidney, brain, vascular endothelial and smooth muscle cells, tracheal and bronchial smooth muscle and the adrenal glands of many mammalian species, including man. This would suggest that ANF influences blood pressure and volume homoeostasis by affecting any one of a number of biochemical or physiological mechanisms via different target tissues. ANF is now considered a potentially valuable therapeutic agent for the treatment of hypertension and congestive heart failure. Synthesis of potent receptor antagonists could be extremely useful in the treatment of various clinical situations which are produced or complicated by endogenously produced ANF, such as chronic orthostatic hypotension.

Notes: Summary Isolated kidneys of Wistar rats and spontaneously hypertensive rats (SHR) were perfused with Tyrode's solution. In 2- and 6-month old SHR, the maximal increase in perfusion pressure caused by norepinephrine was higher than in 2- and 6-month old Wistar rats, but the sensitivity, as judged from the dose of the agonist required to reach 50% of the maximal response was the same. Both the maximal response and the sensitivity to serotonin were significantly augmented in 6-month old SHR and Wistar rats when compared to the young animals. This hypersensitivity was more pronounced in SHR than in Wistar rats. Infusion of serotonin potentiated the vasoconstriction induced by a bolus of norepinephrine. This amplification, due to activation of S2-serotonergic receptors, was more pronounced in the old animals. No amplification occurred when norepinephrine was infused instead of serotonin. Tachyphylaxis to the amplifying effect of serotonin was observed and was less pronounced in kidneys from old than from young animals. The amplifying effect of serotonin was inhibited by ketanserin at concentrations which did not, or only moderately, inhibit the response to norepinephrine.

Notes: Summary In 50 patients without renal insufficiency, fibrinolytic activity, as reflected by euglobulin lysis time, was determined in blood obtained from the renal veins, the renal artery and a peripheral vein. Fibrinolytic activity was found to be significantly higher in the renal veins than in the renal artery and the peripheral vein. Other coagulation and fibrinolysis parameters did not show such differences. In addition, a patient with acute oligoanuric renal failure was investigated. This patient demonstrated reduced overall fibrinolytic activity, but there were no differences between the activity in the blood of the renal veins and that of the renal artery or peripheral vein. It seems, therefore, that the kidneys release plasminogen activators into the systemic circulation. This may be decreased in renal failure, probably contributing to the well-known diminished fibrinolysis in some kidney diseases.

Notes: Summary The proximal tubule cell is the major site of renal ammoniagenesis. Glutamine is the major substrate. Deamidation by mitochondrial glutaminase yields glutamate− and NH 4 + (not NH3, as traditionally taught). A second NH 4 + ion is obtained by deamination of glutamate− to 2-oxo-glutarate2−. NH 4 + preferentially enters the tubule lumen primarily, but probably not exclusively, by non-ionic diffusion of NH3. For each NH3 formed in the cell one H+ ion is left behind. H+ and NH3 are secreted on separate routes, but recombine in the lumen to NH 4 + and reach the final urine in this form. This processper se does not net-remove H+ from the organism. For this purpose, the anionic products of ammoniagenesis (2-oxo-glutarate2− and others) have to be converted into neutral compounds (CO2, glucose). This metabolism again takes place usually in the tubule cell. For each negative charge one HCO 3 − is formed which enters the peritubular blood. Luminal γ-glutamyl transferase-mediated ammoniagenesis contributes to NH 4 + accumulation in the proximal tubule to a small extent. The endproximal NH 4 + delivery exceeds the filtered load by a factor of 9. Only 1/3 of it reaches the distal convoluted tubule mainly because NH 4 + as such is reabsorbed from the thick ascending limb of Henle's loop by secondary active transport or electrodiffusion. Both processes are energized by the active Na+ transport in this segment. Thereby NH3↔NH 4 + is accumulated in the medullary interstitium, which establishes the chemical gradient for non-ionic diffusion of NH3 into the lumen of the collecting ducts. This is favoured by the acidic disequilibrium pH in the lumen of this segment. Secretion of NH3↔NH 4 + , probably by non-ionic diffusion, also into the descending limb of the loop is hypothesized to maintain (together with the NH 4 + reabsorption in the thick ascending limb) the high interstitial NH3↔NH 4 + concentration increasing towards to inner medulla. Thus, the principle of counter current multiplication seems to be involved also in NH 4 + excretion.

Notes: Summary The aim of this study was to investigate the influence of acid and alkali food supplementation on systemic ammonemia to explain the hyper-ammonemia previously observed in rats fed a high protein diet. In normal rats, arterial ammonia concentration significantly increases after 4 days of HCl-supplemented diet. Following a NaHCO3-enriched food, there is only a slight but not significant decrease in arterial ammonia level. These changes occur before any variation in arterial acid-base status and are of renal origin. Indeed, there is a positive linear correlation (r = 0.946;P 〈 0.001) between arterial ammonia level and the ammonia concentration difference between the renal vein and artery (which varies proportionally to the urinary ammonium excretion). Hindquarter uptake and intestinal release of ammonia do not significantly participate in the arterial ammonia changes observed. Following HCl-enriched diets, increased renal glutamine uptake, enhanced hindquarter glutamine release, and perhaps decreased intestinal glutamine uptake occur simultaneously. In conclusion, acid and alkali food supplementation intervenes on the renal ammonia release into the circulation with concomitant arterial ammonemia changes.

Notes: Summary In the kidney of two elasmobranch fish, the little skate (Raja erinacea) and the spiny dogfish (Squalus acanthias), each tubular bundle is wrapped by a continuous sheath of extremely flattened cells which are ordered in several closely superimposed layers. Thin sections and freeze-fracture replicas demonstrate that extensive tight functions exist between the cells of this peritubular sheath. The sheath cells lie on a discontinuous basement membrane which suggests that they do not belong to the connective tissue. Conceivably, each peritubular sheath segregates the milieu inside the sheath (surrounding the bundle of 5 tubules bules and capillaries which form the countercurrent system) from the milieu outside the sheath (connective tissue matrix in which the bundles are embedded).

Notes: Summary The kidney of a 7-month-old male Cairn terrier with globoid cell leukodystrophy (GLD) was investigated with light and electron microscopes. A few tubular epithelial cells in the inner medulla as well as some exfoliated cells in the lumina revealed PAS-positive cytoplasm in which needle-like structures were to be seen on occasion. At the ultrastructural level, characteristic inclusions of GLD were found in these cells. This observation indicates that in addition to our previous report in the kidney of murine GLD (Takahashi et al. 1984), kidney in canine GLD also is a site of abnormal storage of galactosylceramide, although so far no morphological or biochemical evidence of galactosylceramide storage was demonstrated in human GLD

Notes: Abstract In isolated perfused segments of the mouse proximal tubule, the potential difference across the basolateral cell membrane (PDbl) was determined with conventional microelectrodes. Under control conditions with symmetrical solutions it amounted to −62±1 mV (n=118). The potential difference across the epithelium (PDte) was −1.7±0.1 mV (n=45). Transepithelial resistance amounted to 1.82±0.09 kΩ cm (n=28), corresponding to 11.4±0.6 Ω cm2. Increasing bath potassium concentration from 5 to 20 mmol/l depolarized PDbl by +24±1 mV (n=103), and PDte by +1.6±0.1 mV (n=19). Thus, the basolateral cell membrane is preferably conductive to potassium. Rapid cooling of the bath perfusate from 38°C to 10°C led to a transient hyperpolarization of PDbl from −60±1 to −65±1 mV (n=21) within 40 s followed by gradual depolarization by +18±1% (n=14) within 5 min. The transepithelial resistance increased significantly from 1.78±0.11 kΩ cm to 2.20±0.21 kΩ cm (n=15). Rapid rewarming of the bath to 38°C caused a depolarization from −61±2 mV (n=17) to −43±2 mV (n=16) within 15 s followed by a repolarization to −59±2 mV (n=10) within 40 s. Ouabain invariably depolarized PDbl. During both, sustained cooling or application of ouabain, the sensitivity of PDbl to bath potassium concentration decreased in parallel to PDbl pointing to a gradual decrease of potassium conductance. Phlorizin hyperpolarized the cell membrane from −59±2 to −66±1 mV (n=13), virtually abolished the transient hyperpolarization under cooling, and significantly reduced the depolarization after rewarming from +17±2 mV (n=16) to +9±3 mV (n=9). The present data indicate that the contribution of peritubular potassium conductance to the cell membrane conductance decreases following inhibition of basolateral (Na++K+)-ATPase. Apparently, cooling from 37° to 10°C does not only reduce (Na−+K+)-ATPase activity but in addition luminal sodium uptake mechanisms such as the sodium glucose cotransporter. As a result, cooling leads to an initial hyperpolarization of the cell followed by depolarization only after some delay.

Notes: Abstract The kinetics of sulfate uptake were studied in basolateral membrane vesicles from rat renal cortex. Sulfate uptake exhibits a DIDS-sensitive, saturable component, and a DIDS-insensitive component, which does not saturate in the tested sulfate concentration range (up to 10 mM). Intravesicular (= trans) sulfate strongly stimulates sulfate uptake by increasingJ max and — to a lesser degree — by decreasing apparentK m. The marked dependence ofJ max on trans-sulfate indicates that the transport system operates as an anion exchanger. Half-maximal sulfate uptake occurs at 0.08–0.14 mmol/l extravesicular sulfate. Half-maximal trans-stimulation is observed at 11 mmol/l intravesicular sulfate indicating that the sulfate transporter is highly asymmetric. Lowering extravesicular pH stimulates sulfate uptake, suggesting that external protons are essential for sulfate uptake. This stimulation is mainly due to a decrease inK m. An inside positive membrane potential stimulates sulfate uptake at pHout=8.8, but not at pHout=6.4. These results are compatible with electrogenic sulfate transport at higher and electroneutral 2H+−SO 4 2− cotransport at lower pH.

Notes: Abstract The effect of single (SC) administration of mercuric chloride (1 mg Hg/kg) alone or jointly with (PO) sodium selenite (0.39 mg Se/kg) on kidney disposition of mercury (Hg) and metallothionein (MT) and urinary excretion of Hg, zinc (Zn) and copper (Cu) has been studied in the female rat. The excretion of Hg and essential metals was determined every day following exposure. Daily excretion of endogenous Cu and Zn the Hg-exposed group was about threefold and fourfold, respectively, in comparison with control groups of rats. Sodium selenite prevented the urinary excretion of endogenous Cu and partly of Zn.

Notes: Abstract The distribution of a single low dose of [3H]ochratoxin A (OTA) in different tissues of male Wistar rats, after administration by intubation, was investigated after 5 h, 24 h and 48 h. This dose corresponds to concentrations encountered in naturally contaminated feed (4 ppm). The distribution of [3H]-label varied with the time elapsed after administration; at 5 h the highest specific label was found in the stomach contents and in decreasing order in: intestinal contents, lung, liver, kidney, heart, fat, intestine, testes, and the lowest in muscles, spleen and brain. With exception of brain, fat, stomach and lung, all tissues showed maximum levels at 24 h, after which time the label decreased steadily, whereas in fat it increased. After a 12-week feeding experiment, with doses of 288.8 μg/kg corresponding to an intake of 4 ppm in feed each 48 h, the DNA in liver and kidneys was investigated for damage. By the alkaline elution method combined with micro-spectrofluorimetric determinations of DNA, evidence for DNA single-strand breaks was obtained. These findings support reports on the carcinogenic action of OTA.

Notes: Summary Cell junctions in the renal tubule of the fresh-water rainbow trout were studied with thin-section and freeze-fracture techniques. Gap junctions were restricted to the proximal tubule, which is consistent with other vertebrate classes. Segments I and II of the proximal tubule and the collecting tubule/collecting duct system exhibited a well-developed zonula occludens with anastomosing strands. The distal segment showed a narrow zonula occludens composed of few parallel strands. The structure of the occluding junctions along the renal tubule of this teleost displays several similarities with the pattern of the zonulae occludentes in the amphibian and the mammalian nephron. From these observations, in conjunction with available data from other vertebrate classes, it can be concluded that in the proximal tubule the development of a deep and complex zonula occludens is a general feature of cold-blooded vertebrates.

Notes: Summary Kidneys of pigs with various degrees of induced chronic obstructive nephropathy were studied by light- and electron microscopy to assess the structural changes of proximal convoluted tubules with increasing degrees of atrophy. A particular aim was to evaluate the quantitative relationship between proximal tubular and interstitial changes in early tubular atrophy. The kidneys were subjected to varying degrees of ureteral obstruction and were fixed by in vivo vascular perfusion. Quantitative (morphometric) analyses were carried out on montages of electron micrographs representing randomly selected cortical areas and cross sections of individual proximal convoluted tubules. The results demonstrated that ureteral obstruction was followed by significant reductions in proximal tubular epithelium, in volume of proximal tubular mitochondria and in surface area of proximal tubular basolateral membranes. These changes were present even in the absence of any demonstrable increase in cortical interstitium or alterations in the relationships between proximal tubules and peritubular capillaries. With increase in the volume of cortical interstitium the proximal tubules were further simplified in ultra-structure with a reduced number of interdigitating lateral cell processes. Concomitantly there were significant quantitative changes in the spatial associations between tubules and capillaries due to increase in tubulo-capillary distances. The present study shows that ultrastructural changes in proximal tubules during early atrophy precede the volume increase in cortical interstitium associated with chronic obstructive nephropathy. It is suggested that the early tubular changes are due to decreased functional loads, whereas the further progression of tubular atrophy may be a result of impaired nourishment of the tubular cells due to increased interstitial tissue and altered relationships between tubules and capillaries.

Notes: Summary A new endothelial cell structure, named the endothelial pocket, has been found by combined transmission and scanning electron microscopic studies of renal peritubular capillaries. Transmission EM observations made on these and other fenestrated capillaries demonstrated that each pocket consists of an attenuated fold of fenestrated endothelium that projects 200 nm into the lumen above the rest of the endothelial surface. Beneath this luminal fold, there is a space and then another layer of fenestrated endothelium which abuts the basal lamina. The linear density of endothelial pockets was measured in the capillaries of the kidney cortex, intestinal mucosa and exocrine pancreas in mice and determined to be 0.067, 0.017 and 0.007 pockets·μm-1 respectively. Cationic ferritin decoration of the anionic sites on the luminal surface of the endothelium in these capillary beds revealed that both unlabelled and labelled diaphragms are clustered. In such specimens, the majority of the luminal diaphragms on endothelial pockets did not have cationic ferritin binding sites detectable by either scanning or transmission EM. On this account as well as on account of their general morphology, endothelial pockets appear to be multifold versions of the simple transendothelial channel.

Notes: Summary Histamine N-methyltransferase (S-adenosylmethionine: histamine N-methyltransferase, E.C. 2.1.1.8) was purified to homogeneity from rat kidney, and antibody was raised against it in guinea pigs. The antibody immunoprecipitated histamine N-methyltransferase. Immunofluorescent histochemical studies with anti-histamine N-methyltransferase antibody as the first antibody and goat antiguinea pig IgG conjugated with fluorescein isothiocyanate as the second, showed the presence of immunoreactive structures in the proximal tubules of rat kidney. The brain showed no immunoreaction with the antibody.

Notes: Summary The authors studied the different surgical approaches to the upper urinary tract in children. These approaches are the posterolateral lumbar, posterior and anterolateral lumbar routes. Special emphasis should be given to the anterolateral extraperitoneal approach. This approach in children gives excellent exposure of the kidney and causes minimum disruption of the normal anatomy, thereby yielding very satisfactory functional and cosmetic results

Notes: Summary The renal handling of ethanol comprises glomerular filtration and tubular reabsorption. Due to its high permeability alcohol concentration in the tubular fluid approaches that of peritubular fluid and under steady state conditions alcohol concentration in the final urine is almost the same as in serum water. Even in high concentrations alcohol does not significantly interfere with kidney cell function. This seems to be due to the fact that renal tissue is almost free from alcohol dehydrogenase. Thus, acetaldehyde, the cytotoxic intermediate of alcohol metabolism, is not accumulated in effective dosis. If applied directly in micropuncture experiments alcohol is without distinct effects while acetaldehyde inhibits the main parameters of cellular vitality as measured by electrical membrane potentials and intracellular ion activities.

Notes: Summary A new model for the study of intra-renal reflux (IRR) is proposed. The renal pelvis of human kidneys, either obtained from cadavers or removed surgically, was injected, at increasing pressures, with dye solutions to investigate intra-renal reflux. To reproduce physiological conditions as closely as possible, arterial perfusion was performed, either continuously or by means of a peristaltic pump, so that a predetermined pressure in the vascular system could be obtained. Comparison was made between results obtained by this technique and the results reported in the literature and previously recorded by the present authors without any perfusion of the vascular system. Our results show significant difsion of the vascular system. Our results show significant differences in the threshold of IRR compared to data from experiments in which vascular perfusion was not simultaneously performed. It can be concluded that, under physiological conditions, intrarenal flux occurs at pressures of 40 cm H2O, and pyelovenous reflux at pressures of 60–70 cm H2O.

Notes: Summary The structure of the kidney of the crucian carp (Carassius auratus; a freshwater teleost, Cypriniformes) was studied by means of reconstruction from serial paraffin and semithin sections. In C. auratus, the Wolffian duct traverses the entire kidney. At various levels collecting ducts of different length and thickness join the Wolffian duct at right angles. Each collecting duct accepts a large number of connecting tubules, which are established by the joining of many nephrons. A regular pattern concerning the distribution of nephrons and the fusion of renal tubules is not apparent. Four segments have been distinguished in renal tubules; 1) proximal tubule, 2) distal tubule, 3) connecting tubule and 4) collecting duct. A neck and an intermediate segment are absent. The proximal tubule is established by proximal tubule cells which bear a brush border and have a conspicuous apical cytoplasmic rim containing few cell organelles, ciliated cells, mucous cells and dark cells. In the first part of the proximal tubule the brush border and the apical cytoplasmic rim of proximal tubule cells are well developed. Ciliated cells are interposed between proximal tubule cells, decreasing in number toward the end of this part. In the second part ciliated cells are absent and dark cells are numerous. In the third part the brush border and the apical cytoplasmic rim of proximal tubule cells are scarcely developed. Ciliated cells reapear and increase in number toward the distal tubule. The distal and connecting tubule are similar in epithelial structure. Connecting tubules are joined distal tubules and thus they belong to two or more nephrons. The main cells of distal and connecting tubules contain abundant mitochondria, but have no brush border. The connecting tubule becomes a collecting duct before joining the Wolffian duct. The main cells of collecting ducts are characterized by division of their cytoplasm into a dark apical half and a light basal half.

Notes: Summary In a 61-year-old woman, who had been exposed for 20 years to cadmium in the production of Ni-Cd batteries, nephrectomy of the contracted kidney was performed. The removed kidney was examined histologically and the cadmium concentration was determined in the cortex (44.97 μg g−1) and in the medulla (7.71 μg g−1). The homogenates of the renal cortex and medulla were subjected to gel filtration on Sephadex G-75. In the cortex, as well as the medulla, cadmium was predominantly found in the low-molecular (metallothionein) fraction, but in the cortex, Cd content in this fraction was six times higher than in the medulla. The determination of SH groups and proteins in high- and low-molecular fractions indicates an induction of the metallothionein formation primarily in the renal cortex.

Notes: Summary The present autoradiographical study examines the distribution of the two β-adrenoceptor subtypes in sections of rat and guinea-pig kidney. The radioligand [125Iodo]-(-)-cyanopindolol was used for the labelling of β-adrenoceptors and the selective β-adrenoceptor blocking agents ICI 89-406 (β1-antagonist) and ICI 118-551 (β2-antagonist) were utilized to differentiate both subclasses unequivocally. β-Adrenoceptors in rat kidney were found to be almost exclusively β1. They were located mainly on glomeruli and to a lesser extent on the straight part of the distal tubules and on the cortical portion of the collecting ducts. Some β2-adrenoceptors were localized around the corticomedullary junction. Grain localization in the autoradiograms was absent in the inner medulla and papilla. Glomeruli and distal tubules of the guinea-pig kidney also possess only β1-adrenoceptors, but, in contrast to the rat, extremely high concentrations of β2-adrenoceptors were associated with the straight part of the proximal tubules in the cortex and possibly with the cortical portion of the collecting duct. Labelling was not detected on the proximal convoluted tubule in either species.

Notes: Summary Maleate causes an enhanced excretion of amino acids, glucose, phosphate and bicarbonate. In addition to this inhibition of fluid and electrolyte reabsorption malate decreases glomerular filtration rate (GFR). The present investigation was designed to study the mechanisms of this fall in GFR. In group I (Sprague-Dawley rats;N=8) maleate (2 mmol/kg body weight i.v.) increased the hydrostatic pressure in proximal tubule from 12.6±0.5 to 16.3±0.8 mm Hg (mean+SEM) and stop flow pressure in the first accessible loop of the proximal tubule was unchanged (33.6±0.4 vs 33.1±1.3 mm Hg; n.s.). Directly measured hydrostatic pressure in the glomerular capillaries in Munich-Wistar rats (N=7), however, was reduced by maleate from 47.6±1.6 to 42.4±1.9 mm Hg. In group II (N=8) we determined single nephron filtration rate (SNGFR) from distal and proximal collection sites in the same nephron in a paired fashion under control conditions and after maleate administration to assess the activity of the tubuloglomerular feedback. In the control periods SNGFR (16 nephrons) from distal collection sites was 26.3±1.6 nl/min whereas SNGFR from proximal collection sites was 31.8±2.4 nl/min. Following maleate distal SNGFR (17 nephrons) was 15.2±1.7 nl/min and proximal SNGFR was 24.3±2.2 nl/min. The ratio distal/proximal SNGFR was 1.23±0.07 under control conditions and increased to 1.76±0.1 following maleate indicating enhanced activity of tubuloglomerular feedback. Following maleate (group III;N=8) the chloride concentration in the late proximal tubular fluid fell from 135±4 mmol/l to 121±6 mmol/l (13 tubules), however, in the early distal tubule we found an increase in chloride concentration from 43±3 mmol/l to 62±6 mmol/l (12 tubules). Delivery of chloride to the loop of Henle was 2,107±221 pmol/min in the control periods and decreased to 1,475±200 pmol/min during maleate. Since early distal chloride delivery increased from 199±24 pmol/min to 364±47 pmol/min following maleate inhibition of chloride reabsorption in the loop of Henle has to be assumed. We conclude that maleate decreases glomerular filtration rate first by an elevation of hydrostatic pressure in the proximal tubule which is the result of inhibition of fluid and electrolyte reabsorption, and second by activation of the tubuloglomerular feedback.

Notes: Abstract To compare the activity of Na−K-ATPase in the red blood cells (RBCs) and in renal tissue in disorders of Na+ metabolism, the following groups of rats were studied: 1) control, intact rats, 2) adrenalectomized (ADX) rats, 3) intact rats treated with DOCA, 4) ADX DOCA-treated rats, 5) intact salt-loaded rats, 6) ADX salt-loaded rats, 7) intact dexamethasone-treated rats (DEXA), and 8) ADX DEXA-treated rats. After adrenalectomy (group 2) serum Na1 decreased and serum K+ increased. Renal Na−K-ATPase in cortex, medulla and papilla of the control group was 44±2.7 μmol Pi/mg prot/h, 128.2±5.9 and 44±3.2 respectively and in group 2 the enzyme activity was 32.5±2.0 (P〈0.005), 81.7±4.5 (P〈0.001) and 23.6±1.9 (P〈0.001) respectively. RBCs Na−K-ATPase of control animals was 2.82±0.19 μmol Pi/mg prot/h, while in group 2 the activity was 1.43±0.24 (P〈0.001). DOCA treatment of ADX rats (group 4) normalized serum electrolytes and Na−K-ATPase activity in the renal cortex and papilla and in the RBCs. In the renal medulla the correction by DOCA was only partial. Salt loading of ADX rats (group 6) normalized serum electrolytes and Na−K-ATPase activity in the renal medulla and RBCs. Salt loading of normal rats increased RBC Na−K-ATPase to 3.72±0.36 (P〈0.02) and medullary Na−K-ATPase to 185.6±9.8 (P〈0.01). DEXA treatment of ADX rats (group 8) corrected only partially the abnormalities in serum electrolytes and Na−K-ATPase activity in the kidney and in the RBCs. These findings show, 1) parallel changes in the activity of Na−K-ATPase in the RBCs and in the kidney after adrenalectomy, 2) parallel changes in the enzyme activity in RBCs and in the kidney medulla after salt loading, and 3) correction towards normal of RBC Na−K-ATPase after ADX by NaCl and DOCA treatment.

Notes: Abstract The uptake of cytidine, of thymidine and of uridine in brush border vesicles prepared from the cortex of rat kidney has been studied by the technique of rapid filtration. The nucleosides were not metabolized in the vesicles. The time-courses of uptake in the presence of inwardly directed gradients of Na+ and of K+ showed an overshoot, indicating uphill transport. The overshoot was much more pronounced with Na+ than with K+; it was not observed when Na+ was at equilibrium across the membrane. The uptake of the nucleosides was stimulated by an inside negative potential in the presence of Na+. These results provide evidence for a cotransport of pyrimidine nucleosides with Na+. The apparentK m's for the uptake of cytidine, of thymidine and of uridine were 3.76 μmol · l−1, 4.18 μmol · l−1 and 7.21 μmol · l−1 respectively. The uptake of the pyrimidine nucleosides was insensitive to 6-nitrobenzylthioinosine. This insensitivity as well as the high affinity for the nucleosides and the capacity for uphill transport indicate that the nucleoside carrier(s) is renal brush border is (are) different from the carriers found in most other cell types.

Notes: Abstract In the present study the formation and the effects of cyclophosphamide-derived acrolein were investigated using isolated cells from rat liver and kidney, with particular regard to the protective action of low molecular weight thiols against cellular toxicity. The results may be summarized as follows: (a) Cyclophosphamide (CTX)-mediated toxicity to isolated cells is dependent on cytochrome P-450 activity; (b) Loss of viability in cells incubated with cyclophosphamide is preceded by a depletion of cellular GSH; (c) Stimulation of cellular GSH synthesis or the presence of low molecular weight thiols in the incubation medium protects against cyclophosphamide-induced toxicity; (d) Acrolein is probably formed extracellularly as well as intracellularly and can be detoxified by thiol compounds, forming a thiochemiacetal or a thioether.

Notes: Abstract In acute studies, approximately 70–90% of cytosolic cadmium in liver and kidney has been shown to be bound to metallothionein, a low-molecular weight protein. In this study, we report on the influence of dietary selenium on the distribution of cadmium in rat kidney and liver. Contrary to the findings of most acute studies, our results indicate that only a relatively small proportion of cadmium (approximately 14% in the kidney and 44% in the liver) is bound to metallothionein when cadmium is administered for 7 weeks in the diet and via osmotic minipumps to selenium-deficient rats. Feeding rats the same diet supplemented with 1.0 ppm selenium results in no detectable cadmium-metallothionein peak in the kidney, and only about 10% of the cytosolic cadmium elutes as cadmium bound to metallothionein in the liver. In animals fed the selenium-supplemented diet, the bulk of the cadmium is recovered in the low-molecular weight fraction. Dietary selenium did not significantly affect the distribution of zinc and copper in the kidney or liver.

Notes: Abstract In this study the concentrations of cadmium, zinc and copper were determined by atomic absorption spectrophotometry in 51 post mortem kidney cortex samples. A histopathological examination of the kidney was also performed. These parameters, together with age and smoking habit, were statistically related by means of factor analysis. The results show that the first factor associated smoking habit, cadmium and zinc and the second factor histopathological findings and age.

Notes: Abstract Uterine hyperemia in a menstruating adolescent girl was visualized on a renal transplant evaluation. This mimicked early excretion into the urinary bladder.

Notes: Summary We studied the distribution of gentamicin in the inner ear, brain and kidney of the guinea pig following intraperitoneal administration or perfusion of gentamicin through the perilymphatic space. The resulting histopathologcial changes were examined by immunofluorescence using antigentamicin antiserum. After perfusion of gentamicin through the perilymphatic space, specific fluorescence was found in the cochlea, and was especially prominent in the outer hair cells, basilar membrane and basilar crest. Although no fluorescence was observed in the cochlea following intraperitoneal administration of high doses of gentamicin, type I hair cells in the vestibule were seen to be selectively stained with the antibody. Furthermore, some of the vestibular ganglion cells, Purkinje cells and unidentified nuclei in the brain stem were also stained. In particular, fine granules showing relatively intense fluorescence were recognized in the cytoplasm of the stained cells. In the cortex of kidney, only proximal tubular cells were stained with intense fluorescence. Our results suggest that the aminoglycoside antibiotics have two sites of action: one is the cell membrane of the sensory hair cells and the other is the cytoplasm.

Notes: Abstract A mathematical model is presented which provides an overall description of the renal/body fluid system, comprising an interconnected set of physiologically based representations of the relevant subsystems of the human organism. The model is used to test a number of hypotheses relating to the dynamics and control of the human renal system, including dynamics of ADH clearance, glomerular tubular balance and the control of the rate of release of ADH. Results are presented establishing the validity of the model in a number of empirical tests.

Notes: Summary A study of the distribution of sulfadimethoxine and sulfisoxazole in plasma, kidney cortex and medullopapillary tissue is presented. Equimolar amounts of each sulfonamide were fed to separate groups of hydropenic rats, and measurements carried out after one hour and five hours. Similar plasma concentrations of either drug were encountered one hour after the ingestion. A significant increase in the plasma concentration of sulfadimethoxine and a significant decrease in the plasma concentration of sulfisoxazole were observed five hours after ingestion. There was no change in the kidney tissue/plasma concentration ratios between one and five hours after the ingestion of sulfadimethoxine or sulfisoxazole. However, the ratios were significantly higher for sulfisoxazole, a fact that can be explained by its higher renal excretion rate. Likewise, the significant higher cortico-papillary concentration gradient observed for sulfisoxazole is interpreted to be a result of its slower rate of back diffusion in the distal segments of the nephron (on account of its lower pKa) and in contrast to sulfadimethoxine to the lack of active reabsorption of sulfisoxazole.

Notes: Summary In conscious, moderately hydrated female rabbits the effect of NaCl,l-alanine,l-serine,l-cysteine, 2,3-dimercapto-1-propanol, S-(2-aminoethyl)-isothiouronium, Na2S2O3, S-methyl-l-cysteine andd-penicillamine upon renal secretion of water and osmotically active substance was investigated. All compounds, except NaCl,l-alanine andl-serine, caused a decrease of urine volume and an increase of osmolarity. The effect is similar to that of the antidiuretic hormone and is dependent upon the presence of the SH-group.

Notes: Summary With the aim of studying the effect of the tubular Na+-load and of the type of anion on the renal Na+-reabsorption the following experiments were carried out using isolated artificially perfused kidneys of Rana ridibunda. 1. Variation of the tubular Na+-load by changing the concentration of NaCl in the perfusion fluid. 2. Variation of the tubular Na+-(Cl−)-load by changing the rate of glomerular filtration (GFR) by means of altering the perfusion pressure. 3. Determination of the rate of Na+-reabsorption if Na+ is offered in the form of Na-cyclamate, a Na+-salt with a large and slowly penetrating anion. 4. Determination of the rate of Na+-reabsorption at tubular Na+-loads consisting to 33% of NaHCO3 and to 66% of NaCl. The following results were obtained: 1. At NaCl-concentrations in the perfusion fluid above 76.5 mMol/l the rate of Na+-reabsorption remains constant. The fractional reabsorption at low Na+-concentrations is great, it is low at high Na+-concentrations. The phenomenon of glomerulo-tubular balance only applies to a medium range. 2. Raising the tubular Na+-load by increasing the GFR results in a significantly larger increase of the fractional Na+-reabsorption than does raising the tubular Na+-load by increasing the Na+-concentration. Raising the tubular Na+-load above 32 μMol/min · kg does not lead to a further increase of Na+-reabsorption. Here also glomerulo-tubular balance is maintained only within a medium range. 3. At concentrations of Na+-cyclamate above 38.25 mMol/l the rate of Na+-reabsorption remains constant. With increasing concentrations of Na+-cyclamate the fractional Na+-reabsorption decreases. 4. Above a total Na+-concentration of 114.75 mMol/l (66.6% NaCl and 33.3% NaHCO3) the rate of Na+-reabsorption remains constant. The fractional reabsorption of Na+ under these conditions reaches a maximum at a Na+-concentration of 76.5 mMol/l. The rate of Na+-reabsorption depends largely on the filtered Na+-load. However, the quantity of Na+ reabsorbed is higher if the Na+-load is raised by increasing the GFR instead of by raising the Na+-concentration in the perfusion fluid. Under all experimental conditions studied the tubular reabsorption of Na+ is limited at different but definite levels. The type of anion influences the rate of Na+-reabsorption in so far as large anions (cyclamate) decrease the reabsorption of Na+ at a given tubular Na+-load. Presumably the observed increase of Na+-reabsorption in the presence of NaHCO3 is the result of a cellular alkalinisation due to the bicarbonate.

Notes: Summary Four weeks after clamping one renal artery, mean arterial blood pressure averaged 200 mm Hg.86Rubidium-uptake 2 min after intravenous injection, was measured in the renal cortex and in different slices of renal medulla. As estimated by this method, blood flow of the untouched kidney which is exposed to the high blood pressure was unchanged in the cortex. Blood flow in the outer medulla was elevated by 40%, in the inner medulla by 50% and in the papilla by 70% when compared with the clamped kidney. Total and regional blood flow of the clamped kidney was not statistically different from kidneys of normotensive controls. Cardiac output was not changed in hypertension. Inulin and PAH clearance were normal in both the untouched and in the clamped kidney. Tissue osmolality of inner medulla and papilla was lower in the untouched than in the clamped kidney. Sodium concentration in inner medulla and papilla of the untouched kidney was slightly higher than in the clamped kidney. It is concluded that in chronic hypertension, autoregulation of blood flow through the medulla is not maintained. The increased medullary blood flow may be responsible for the elevated urinary excretion of the untouched kidney in chronic hypertension.

Notes: Zusammenfassung Untersucht wurde die Funktion der juxtamedullären Nephrone (Mikropunktion der langen Henleschen Schleifen an der freigelegten Papille) an normalen Ratten und an der ungeklammerten Niere von Ratten mit experimentellem Hochdruck (einseitige Goldblatt-Klammer). Mit steigendem Blutdruck (von 90–190 mm Hg) wurde eine kontinuierliche Zunahme des juxtamedullären Einzelnephronfiltrates beobachtet. Es betrug im Mittel 60·10−6 ml/min/g Niere bei der Kontrollgruppe (mittlerer arterieller Blutdruck 116 mm Hg) und 114·10−6 ml/min/g Niere bei der hypertensiven Gruppe (mittlerer arterieller Blutdruck 164 mm Hg). Das Einzelfiltrat oberflächlicher Nephrone änderte sich nicht; es betrug 30·10−6 ml/min/g Niere. Das Glomerulumfiltrat der gesamten Niere nahm geringfügig von 1,07 auf 1,28 ml/min/g Niere zu. Sowohl bei den normotensiven wie bei den hypertensiven Tieren waren TF/P-Inulin-Quotient und intratubuläre Stromstärke im auf- und absteigenden Schenkel der Henleschen Schleife statistisch nicht voneinander zu unterscheiden. Die intratubuläre Stromstärke war im Mittel bei den hypertensiven Tieren doppelt so hoch wie bei der Kontrollgruppe; die TF/P-Inulin-Quotienten waren in beiden Gruppen statistisch nicht voneinander verschieden. Die Ankunftszeit von Lissamingrün in den langen Henleschen Schleifen und in den Sammelrohren war bei den hypertensiven Tieren verkürzt. Die Befunde weisen darauf hin, daß keine Autoregulation des juxtamedullären Glomerulumfiltrates besteht. Es wird angenommen, daß die Erhöhung des juxtamedullären Filtrats zu der vermehrten Harnausscheidung der ungeklammerten Niere von hypertensiven Ratten beiträgt.

Notes: Summary Transtubular absorption of Na and Cl, and intracellular ion concentrations were evaluated in toad kidneys perfused with solutions containing K and without K, and in the presence of 1 mM Ouabain and 1 mM Ethacrynic acid. The following values were obtained with 8.5 mM K: Transtubular absorption of Na and Cl∼68% (percent of filtered load); cell content 294 μmole Na, 433 μmole K, 100 μmole Cl/g solids. Lack of K in the perfusate diminished transtubular absorption to ∼25% and the cells gain 244 μmole Na/g solids, and lose an equimolecular quantity of K. The process is reversible upon raising the K concentration in the perfusate. Ouabain inhibits transtubular absorption to ∼6%; the cells lose about 110 μmole K/g solids, but cellular Na is maintained at the control levels. Ethacrynic acid inhibits transtubular absorption to ∼3%; the cells approximately double their Na and Cl content, but their K is maintained at the control levels. These observations cannot be explained exclusively in terms of an effect on the distal tubule. Probably proximal as well as distal tubules are involved. A single Na pump seems insufficient to account for all experimental findings. The existence of two separate pumps is therefore proposed.

Notes: Summary 3–4 weeks after clamping of one renal artery and nephrectomy of the contralateral kidney the reabsorption of water, sodium and potassium was studied in the different parts of the nephron. Despite clamping, the kidney was enlarged. Water and sodium excretion per g kidney was not significantly increased. Glomerular filtration rate and single nephron filtrate per g kidney, transit time of Lissamine Green through the proximal tubule and through Henle's loop and fractional water reabsorption up to the end of the distal tubule were normal. Contrary to earlier investigations on the clamped kidney without contralateral nephrectomy, there was a normal decrease of sodium concentration and a normal increase of potassium concentration along the distal tubule. We believe that the normalization of distal tubular function in the clamped kidney after nephrectomy of the contralateral kidney is due to the normalization of the renin content. It is suggested that the intrarenal renin resp. angiotensin concentration has a direct inhibitory effect on the sodium reabsorption in the distal tubule, opposite to the effect of aldosterone.