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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 60 (1982), S. 1245-1248 
    ISSN: 1432-1440
    Keywords: Chronic salt loading ; Volume expansion ; Glomerular filtration rate ; Tubuloglomerular feedback ; Humoral substances in tubular fluid ; Chronische Salzbelastung ; Volumenexpansion ; Glomeruläre Filtrationsrate ; Tubuloglomeruläre Rückkoppelung ; Humorale Substanzen in tubulärer Flüssigkeit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei normalem Extrazellulärvolumen reduziert der Harnfluß durch das macula densa Segment der Henle'schen Schleife die glomeruläre Filtrationsrate durch ein Signal aus dem juxtaglomerulären Apparat (tubuloglomerulärer Rückkopplungsmechanismus, TGF). Bei Vergrößerung des Extrazellulärvolumens wird dieser Mechanismus gehemmt, so daß die glomeruläre Filtrationsrate ansteigt. Um festzustellen, ob diese Hemmung durch Veränderungen im juxtaglomerulären Apparat oder in der Tubulusflüssigkeit verursacht wird, wurden an zwei Gruppen von Ratten, deren Extrazellulärvolumen entweder normal war oder durch kochsalzreiche Ernährung expandiert wurde, Austauschversuche mit spätproximaler Tubulusflüssigkeit durchgeführt. Die Tubulusflüssigkeit wurde mit Mikrosaug/Perfusionspumpen gesammelt. Ihre Wirkung auf den TGF wurde geschätzt, indem Henle'sche Schleifen einzelner Tubuli mit 40, 10, und 0 nl/min perfundiert wurden, während gleichzeitig der Harnfluß (EPF) in einem glomerulusnahen Segment des jeweiligen proximalen Tubulus gemessen wurde. Insalzreich ernährten Tieren war die EPF von der Schleifenperfusionsrate unabhängig, wenn die Henle'schen Schleifen mithomologer Tubulusflüssigkeit perfundiert wurden. Mit Tubulusflüssigkeit aussalzarm ernährten Tieren und einer Schleifenperfusionsrate von 40 nl/min fiel die EPF jedoch um etwa 50% gegenüber dem Kontrollwert bei nichtperfundierter Schleife ab. Insalzarm ernährten Tieren, deren Henle'sche Schleifen mithomologer Tubulusflüssigkeit und einer Rate von 40 nl/min perfundiert wurden, fiel die EPF um etwa 50% gegenüber dem Kontrollwert bei nicht perfundierter Schleife ab. Mit Tubulusflüssigkeit aussalzreich ernährten Tieren war die EPF von der Schleifenperfusionsrate unabhängig. Es wird gefolgert, daß der TGF in volumenexpandierten Tieren durch eine Substanz in der Tubulusflüssigkeit gehemmt wird.
    Notes: Summary Experiments were carried out in Wistar rats to determine whether the loss of sensitivity of the tubuloglomerular feedback mechanism (TGF) which is known to occur in volume expansion is due to a change in the functional characteristics of the juxtaglomerular apparatus or to a change in some property of the tubular fluid which influences the feedback signal at the macula densa. Proximal tubular fluid was collected by means of a microperfusion/suction pump from Wistar rats maintained for a minimum of 10 days on a high salt diet and also from rats fed a control low salt diet. Both fluids were then used to perfuse loops of Henle in rats from both groups and the feedback response assessed from the change in early proximal tubular flow rate (EPF). In high salt rats, perfusion of the loop of Henle with homologous tubular fluid confirmed the loss of sensitivity of the TGF mechanism in volume expansion, the response of EPF was practically absent. In contrast, the low salt rat responded with a 50% decrease in EPF to loop perfusion at 40 nl/min with its homologous fluid. On the other hand, when the loop of Henle in high salt rats was perfused at 40 nl/min with heterologous (low salt) tubular fluid, EPF again decreased by some 50% whereas EPF in low salt rats failed to respond to loop perfusion with high salt fluid. From these results it is concluded that in rats chronically volume expanded by a high salt diet an unknown inhibitory principle occurs in the proximal tubular fluid which reduces the sensitivity of the tubuloglomerular feedback mechanism.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 411 (1988), S. 322-327 
    ISSN: 1432-2013
    Keywords: Tubuloglomerular feedback ; Juxtaglomerular apparatus ; Glomerular filtration rate ; Acute volume expansion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Loss of sensitivity or “resetting” of tubuloglomerular feedback has been reported after both acute and chronic volume expansion in rats. In chronic volume expansion due to dietary salt loading, resetting was found to result from the appearance of an inhibitory factor in tubular fluid. The aim of the present study was to test the possibility that resetting after acute isooncotic volume expansion may also be due to such an inhibitor. Rats were acutely volume expanded (4.5% of body weight) by infusion of a solution of fresh plasma and Ringer's solution. Tubuloglomerular feedback activity was assessed in expanded and control animals by measuring early proximal flow (EPF) rate during perfusion of the loop of Henle at varying rates with proximal tubular fluid harvested from the control (control TF) and expanded animals (AVE TF). When loops of Henle in control animals were perfused with control TF at 10, 20 or 40 nl min−1, EPF fell from (mean ±SD) 29.8±5.6 at zero loop flow to 27.5±7.5, 21.1±4.2 and 15.5±4.5 nl min−1 gKW−1 respectively. Perfusion at the same rates with control TF in expanded animals reduced EPF from 39.5±9.6 (at zero loop flow) to 35.9±11.3, 31.6±4.3 and 22.9±6.8 nl min−1 gKW−1 respectively. When loops of Henle in control animals were perfused with AVE TF, EPF fell from 28.6±9.5 (zero loop flow) to 23.5±8.6, 19.9±8.2 and 15.6±6.5 nl min−1 gKW−1 respectively. Perfusion at these rates with AVE TF in the expanded animals depressed EPF from 36.7±7.8 (at zero loop flow) to 33.6±7.3, 28.6±7.6 and 22.7±8.0 nl min−1 gKW−1 respectively. Since the responses to the two perfusion fluids were the same in each group, it is concluded that there is no inhibitory factor present in AVE TF. Although EPF at each perfusion rate was significantly higher in the expanded animals than in control, the change in EPF per unit change in loop perfusion rate was the same in both groups from which it is concluded that no resetting of tubuloglomerular feedback occurred in the present study.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1440
    Keywords: Renal blood flow ; Macula densa ; Adenosine ; Dopamine ; Tubuloglomerular feedback ; SHR ; Wistar rat ; Glomerular filtration rate ; Autacoids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Following the elementary laws of hemodynamics and the functional characteristics of the renal myogenic and macula densa-mediated (TGF) vascular resistance control mechanisms, TGF-mediated changes of renal vascular resistance are amplified by cooperative changes of the myogenic mechanism. Myogenically induced changes, on the other hand, would be antagonized by TGF. Resetting of renal vascular flow resistance by alterations to the TGF mechanisms might thus be more effective than alterations to the myogenic mechanism. Dopamine and adenosine, two autacoids occurring normally in the tubular fluid, may play a key role in operating such a resetting mechanism. Dopamine and adenosine were found in proximal tubular fluid at concentrations of 10−8 and 0.5 10−6 M respectively. Dopamine inhibits the tubuloglomerular feedback mechanism, this inhibition is antagonized concentration-dependently by adenosine. These effects most likely occur via D1 and A1 receptors and hence by regulation of the adenyl cyclase activity in the macula densa cells. The balance between adenosine and dopamine in tubular fluid appears to be under the control of extrarenal parameters. In normal rats, high dietary salt intake, by influencing the secretion of an unknown adrenal hormone, and inhibition of Na-K-ATPase might be of importance. In spontaneously hypertensive rats unknown genetic parameters may also play a role.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2013
    Keywords: Autoregulation ; Tubuloglomerular feedback ; Renal blood flow ; Glomerular filtration rate ; Plasma renin activity ; Deoxycorticosterone acetate ; Plasma volume ; rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tubuloglomerular feedback (TGF) function and autoregulation (renal blood flow RBF; glomerular filtration rate, GFR; single-nephron glomerular filtration rate, SNGFR) were examined in rats chronically treated with deoxycorticosterone acetate (DOCA) and given isotonic saline to drink. DOCA treatment depressed arterial plasma renin activity, expanded plasma volume by 25% and increased arterial blood pressure. Autoregulation of RBF and GFR was maintained in the DOCA animals above 90 mm Hg and 110 mm Hg respectively, whereby both GFR and RBF were lower than in controls. Micropuncture experiments demonstrated the absence of TGF in the DOCA animals. There was no difference between SNGFR values measured in the distal and proximal tubules, nor was there a significant response of SNGFR when loops of Henle were perfused with Ringer's solution at 20 nl/min. Loop perfusion in control rats with tubular fluid collected in DOCA rats elicited a normal TGF response, showing that TGF inhibition in the DOCA animals is due to changes in the function of the juxtaglomerular apparatus. In contrast to control rats, proximal SNGFR was perfectly autoregulated. These results suggest that TGF is not primarily responsible for autoregulation and that the vasodilatation normally resulting from acute TGF interruption is therefore compensated by some other mechanism such that RBF and GFR are lower than in controls.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2013
    Keywords: Rat ; Renal function ; Micropuncture ; Blood gases ; Anaesthesia ; Thiopentone ; Thiobutabarbitone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The thiobutabarbitone(TB, Inactin)-anaesthetised rat is an extremely widely used preparation for the study of renal function at the whole-organ and nephron levels. The recent withdrawal of TB from the market has made it essential to find an anaesthetic producing experimental conditions as similar as possible to TB to allow comparison of past and future data. Blood gas analysis, clearance and micropuncture studies were therefore performed in rats anaesthetised with TB or the related thiobarbiturate thiopentone (TP) (both 100 mg/ kg body weight) to establish whether the latter meets this requirement. Both barbiturates caused similar transient respiratory depression and acidosis. Mean values (TP versus TB) over the total 8-h observation period for glomerular filtration rate (0.94 versus 1.05 ml/min), urine flow (3.8 versus 4.4 μl/min) and K+ excretion (0.98 versus 1.18 μmol/min) were slightly lower (P〈0.05) in TP rats, whereas renal blood flow (6.26 versus 6.24 ml/min), filtration fraction (0.31 versus 0.34) and Na+ excretion (0.11 versus 0.098 μmol/min) did not differ. The single-nephron filtration rate (SNGFR) (42.1 versus 41.1 nl/min) and fractional reabsorption (42% versus 47%), both measured in the proximal tubule, did not differ, although in the TP group SNGFR rose with time (4.4%/h) whereas the fractional reabsorption did not change significantly; in the TB group SNGFR was constant but fractional reabsorption declined with time (1.5%/h). Fractional reabsorption up to the distal convoluted tubule declined with time, this was more pronounced in the TP group. SNGFR measured at this site did not differ between TP and TB (30.3 versus 30.1 nl/min) but increased with time with TP (2.7%/h). Although renal function under TP is somewhat less stable than under TB, the differences are minor and, given that the latter is also characterised by non-steady-state conditions, it is concluded that TP is a reasonable replacement for TB.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 432 (1996), S. 944-947 
    ISSN: 1432-2013
    Keywords: Key words Anaesthesia ; Chloralose ; Ketamine ; Sodium excretion ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Studies on the mechanisms underlying Na balance in anaesthetized rats are complicated by the fact that the most frequently used barbiturate anaesthetics attenuate or abolish this phenomenon. In the present study we show that a combination of nonbarbiturate anaesthetics: chloralose (140 mg/kg i.v.) and ketamine (30 mg/kg i.m.), preserve the ability of rats to excrete intragastrically applied NaCl loads dose dependently. Thus rats anaesthetized with this regime excreted 86–102% of in- tragastrically applied NaCl whereas rats anaesthetiz- ed with thiobutabarbitone sodium (Inactin) excreted only 20–28%. We conclude that chloralose/ketamine anaesthesia is suitable for studies on Na balance mechanisms.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 306 (1979), S. 287-293 
    ISSN: 1432-1912
    Keywords: 2.4-diamino-6.7-dialkylpteridine ; Diuretics ; Micropuncture ; Tubular transport ; Rat kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The excretion of the diuretic substance DADMP (2.4-diamino-6.7-dimethylpteridine) and of DMP (6.7-dimethylpterin) was studied on single nephrons of the rat kidney using microperfusion and microinjection techniques. In the proximal tubule only DADMP was reabsorbed to a significant degree. Fractional reabsorption rate was independent of the load applied and the permeability constant was found to be 2.2·10−4 cm·s−1. Similar results were obtained in nephrons in which the substances, with inulin, were injected from middle proximal tubular puncture sites and recovered in the urine. DMP appeared in the urine quantitatively and simultaneously with the injected inulin. DADMP recovery, however, was only 20–30% of the injected load during the injection period and after 2 h some 70% was recovered from the urine of both kidneys. The reabsorbed fractions were independent of the loads applied, which varied between 2·10−13 mol·min−1 and 10−9 mol·min−1. A comparison of the microperfusion and the microinfusion data suggests that the reabsorption of DADMP occurs predominantly in the proximal convolution, and it appears that the differences between the renal handling of DMP and DADMP are explicable by their different lipid solubilities.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 375 (1978), S. 9-16 
    ISSN: 1432-2013
    Keywords: Pterins ; Micropuncture ; Tubular transport ; Rat kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rat kidney, the rate of urinary biopterin [biopterin (B), 7,8-dihydrobiopterin (BH2), and 5,6,7,8-tetrahydrobiopterin (BH4)] excretion as measured by Crithidia assay, was found to be at least 3 times greater than the rate at which it is filtered (GFR·PBiopt.). At a renal blood flow of 6.43±1.34 ml/min per g kidney wt., biopterin concentrations in arterial and renal venous blood and plasma were similar [art. blood: 250±50 ng/ml, ren. venous blood: 247.3±50.9 ng/ml, art. plasma: 23.1±5.8 ng/ml, ren. venous plasma: 23.4±6.9 ng/ml (means±S.D.)]. 14C-BH4 and3H-inulin, infused by means of a micropump into late proximal segments of single nephrons at concentrations of 10−4–10−6 mol, were excreted at similar fractional rates (inulin: 0.85–0.97, BH4: 0.87–0.92, total recovery 1.00–1.09 and 0.99–1.11, respectively). Similar results were obtained with 6,7-dimethylpterin, but not with 6,7-dimethyl-5,6,7,8-tetrahydropterin. The latter is reabsorbed at a fractional rate of 0.20 at concentrations of 10−7 and 10−6 mol. In microperfusion studies in isolated proximal tubular segments in vivo et situ, no reabsorption of 6,7-dimethylpterin could be detected. In case of 6,7-dimethyl-5,6,7,8-tetrahydropterin (DMPH4) at concentrations of 5·10−5 and 10−5 mol/l, however, a permeability constant of 2.39·10−5 cm/s has been measured. From the fact that more biopterin leaves the kidney with urine plus venous blood than entered it is concluded that reduced biopterin is synthesized de novo in the kidney. With the exception of DMPH4, all types of biopterin are not significantly reabsorbed, but rather, are excreted into the urine due to an anisotropic permeability characteristic of the nephron.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2013
    Keywords: d-Glucose ; Tubular Transport ; Glomerulotubular balance ; Micropuncture ; Clearance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract d-Glucose transport in the kidney of glucose loaded rats was investigated using clearance and micropuncture techniques. The range of plasma glucose concentration in clearance experiments was 20–140 mmol·l−1 and in micropuncture experiments 17–94 mmol·l−1. 1. During hyperglycemia, the glucose concentration in endproximal tubular fluid was elevated above that in arterial plasma. At plasma concentrations above 60 mmol l−1 intratubular glucose concentration was found to be about 1.2 times higher than in plasma. 2. At endproximal puncture sites TF/Posmol was unity throughout the investigated range of hyperglycemia. 3. Proximal tubular glucose reabsorption during hyperglycemia is close to saturation which is compatible to aK m=10.8 mmol l−1 as determined previously. 4. Passive glucose permeability does not change during hyperglycemia. The permeability constant of 2.03·10−5 cm·s−1 does not differ significantly from that during normoglycemia, 1.9·10−5 cm·s−1. 5. Single nephron glomerular filtration rate (SNGFR) and fluid reabsorption in the proximal convolution (C) were significantly correlated during hyperglycemia (r=0.78,P〈0.001). Fractional volume reabsorption during hyperglycemia was decreased to 0.36 as compared to control, but during hyperglycemia it was not affected by the magnitude of the glucose plasma concentration. 6. During hyperglycemia, proximal tubular glucose reabsorption (TG) was correlated to SNGFR (r=0.64,P〈0.001). This relation became insignificant when the influence of volume reabsorption (C) is controlled for (r=0.17,P〉0.5). However, the significance of the correlation between TG and C persists when the influence of SNGFR is held constant. 7. Calculations indicate that when glucose reabsorption was doubled, et sodium transport was increased about fourfold. 8. In hyperglycemia, renal transport rate (TG), when factored by renal glomerular filtration rate (GFR) seems to be linearly related to glucose plasma concentration. Up to endproximal puncture site 25.5% and by the entire kidney 68.2% of the tubular glucose load were reabsorbed. The difference may be attributed either to glucose transport systems which are localized distal to the proximal convoluted tubules and/or to an inhomogenity of the glucose transport in the different types of nephrons.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 405 (1985), S. S131 
    ISSN: 1432-2013
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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