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  • 11
    ISSN: 1432-1106
    Keywords: In vivo microdialysis ; Astrocytic reaction ; Gliosis ; Brain lesion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In vivo microdialysis is an established tool for sampling extracellular fluid compartments. However, microdialysis faces the problem that the implantation of the probe damages the microenvironment from which measurements are derived. In this study, we examined the expression of basic fibroblast growth factor mRNA and protein at the cellular level after implantation of a microdialysis probe into the dorsal hippocampus and found that 8 h after inserting the probe bFGF mRNA was markedly increased in a relatively large area centered around the probe, involving both the dorsal hippocampus and the overlying cerebral cortex, as revealed by radioactive in situ hybridization. Using nonradioactive in situ hybridization with digoxigenin-labelled riboprobes, combined with immunohistochemistry for glial fibrillary acidic protein we demonstrated that bFGF mRNA was exclusively increased in astrocytes at the probe insertion site. Using immunohistochemistry we also found that bFGF-like immunoreactivity was increased after implantation of the probe close to the lesion site, as shown by an increased number of bFGF immunoreactive nuclear glial profiles. These results provide evidence that the implantation of a microdialysis probe into the brain induces activation of bFGF gene expression in astrocytes associated with nuclear bFGF-like immunoreactivity. We conclude that lesion-induced effects have to be considered when evaluating microdialysis data, and that mechanical trauma to the brain will activate astroglial trophism, as seen from the increased density of astroglial profiles demonstrating bFGF mRNA and protein levels.
    Type of Medium: Electronic Resource
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric nephrology 10 (1996), S. 108-112 
    ISSN: 1432-198X
    Keywords: Key words: Transgenic rat ; Transgene ; Renin ; Angiotensinogen ; Cardiovascular system ; Pharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Transgenic animals are used to study the function, regulation and in vivo expression of genes. The effects of the genes of the renin-angiotension system on blood pressure regulation and hypertension were investigated in transgenic rats. The role of the renin-angiotensin system in the development of cardiovascular hypertrophy or hypertensive renal damage was analysed, as well as its interaction with other hormonal systems, i. e. adrenal steroids. The development of a transgenic rat strain carrying the mouse REN-2 gene has provided a new model of hypertension with systolic blood pressure values of 200 mmHg. This model is characterised by low active plasma renin, hyperproreninaemia and high expression of renin in the adrenal gland and other extrarenal tissues. Transgenic rats with the human components of the renin-angiotensin system expressed the human renin and angiotensinogen proteins which interacted species-specifically in transgenic rats. These transgenic models demonstrate the feasibility of studying the function of candidate hypertension genes in transgenic animals. In the future, further refinements in transgene construction, mutation and modification can be tested in such transgenic animal models.
    Type of Medium: Electronic Resource
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric nephrology 10 (1996), S. 108-112 
    ISSN: 1432-198X
    Keywords: Transgenic rat ; Transgene ; Renin ; Angiotensinogen ; Cardiovascular system ; Pharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Transgenic animals are used to study the function, regulation and in vivo expression of genes. The effects of the genes of the renin-angiotension system on blood pressure regulation and hypertension were investigated in transgenic rats. The role of the renin-angiotensin system in the development of cardiovascular hypertrophy of hypertensive renal damage was analysed, as well as its interaction with other hormonal systems, i.e. adrenal steroids. The development of a transgenic rat strain carrying the mouse REN-2 gene has provided a new model of hypertension with systolic blood pressure values of 200 mmHg. This model is characterised by low active plasma renin, hyperproreninaemia and high expression of renin in the adrenal gland and other extrarenal tissues. Transgenic rats with thehuman components of the renin-angiotensin system expressed the human renin and angiotensinogen proteins which interacted species-specifically in transgenic rats. These transgenic models demonstrate the feasibility of studying the function of candidate hypertension genes in transgenic animals. In the future, further refinements in transgene construction, mutation, and modification can be tested in such transgenic animal models.
    Type of Medium: Electronic Resource
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 424 (1993), S. 199-202 
    ISSN: 1432-2013
    Keywords: Renin/angiotensin system ; Intestine ; Gene expression ; Starvation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The existence of a local renin/angiotensin system in the intestine of mammals is speculative despite the known importance of angiotensin II for water and electrolyte homeostasis. We demonstrate the presence of ren-2 transcripts in the small intestine of DBA/2 mice. The marked expression of the ren-2 gene is blunted tissue-specifically by starvation, corroborating a local renin/angiotensin system in this organ.
    Type of Medium: Electronic Resource
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 163-164 (1996), S. 217-221 
    ISSN: 1573-4919
    Keywords: heart hypertrophy ; transgenic rats ; hypertension ; angiotensin II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract TGR(mREN2)27 is a transgenic rat harboring the murine Ren-2 gene and exhibit fulminant hypertension and marked heart hypertrophy. In order to study the role of angiotensin II in the increase of cardiac mass, these animals were treated with anti-hypertensive and non-antihypertensive doses of the angiotensin II receptor AT1 antagonist Telmisartan for 9 weeks. All doses led to significant reductions of heart hypertrophy detected by the evaluation of the diameter of cardiac muscle bundles. We conclude from this study that cardiac hypertrophy in TGR(mREN2)27 is characterized by an increased volume of cardiomyocytes and an unchanged amount of fibrous tissue and that angiotensin II plays an important role in the mechanisms leading to this phenotype.
    Type of Medium: Electronic Resource
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  • 16
    ISSN: 1432-2013
    Keywords: Renin ; Angiotensin ; Thirst ; Hypovolemia ; Polyethleneglycol ; Saralasin ; Captopril ; Enalapril
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of the renin-angiotensin system as a mediator of water intake, induced by hypovolemia after polyethylene glycol (PEG) injection, was investigated. Blockade of angiotensin I converting enzyme and of angiotensin receptors was used as a pharmacological tool. A significant reduction of water intake was observed when angiotensin 1 converting enzyme was inhibited by captopril and enalapril. In PEG-treated rats with blockade of angiotensin I converting enzyme, hypertonic saline injection continued to elicit substantial drinking. Normalization of low blood pressure by vasopressin infusions in PEG and captopril treated rats did not interfere with the antidipsogenic effectiveness of converting enzyme blockade. The angiotensin II receptor antagonist, saralasin, also reduced PEG-induced drinking although less effectively than converting enzyme inhibitors. We conclude that water intake due to isotonic depletion of the extracellular fluid compartment may depend on the activity of the renin-angiotensin system.
    Type of Medium: Electronic Resource
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  • 17
    ISSN: 1432-0878
    Keywords: Adrenal cortex ; Renin-angiotensin system ; Steroidogenesis ; Electron microscopy ; Morphometry ; Rat, transgenic (mRen2) 27
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Transgenic rats for the murine Ren-2 gene display high blood pressure, low circulating levels of angiotensin II, and high renin content in the adrenal glands. Moreover, transgenic rats possess and increased aldosterone secretion (maximal from 6 to 18 weeks of age), paralleling the development of hypertension. To investigate further the cytophysiology of the adrenal glands of this strain of rats, we performed a combined morphometric and functional study of the zona glomerulosa of 10-week-old female transgenic rats. Morphometry did not reveal notable differences between zona glomerulosa cells of transgenic and age- and sex-matched Sprague-Dawley rats, with the exception of a marked accumulation of lipid droplets, in which cholesterol and cholesterol esters are stored. The volume of the lipid-droplet compartment underwent a significant decrease when transgenic rats were previously injected with angiotensin II or ACTH. Dispersed zona glomerulosa cells of transgenic rats showed a significantly higher basal aldosterone secretion, but their response to angiotensin II and ACTH was similar to that of Sprague-Dawley animals. Angiotensin II-receptor number and affinity were not dissimilar in zona glomerulosa cells of transgenic and Sprague-Dawley rats. These data suggest that the sustained stimulation of the adrenal renin-angiotensin system in transgenic animals causes an increase in the accumulation in zona glomerulosa cells of cholesterol available for steroidogenesis, as indicated by the expanded volume of the lipid-droplet compartment and the elevated basal steroidogenesis. However, the basal hyperfunction of the zona glomerulosa in transgenic animals does not appear to be coupled with an enhanced responsivity to its main secretagogues, at least in terms of aldosterone secretion.
    Type of Medium: Electronic Resource
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  • 18
    ISSN: 1432-0878
    Keywords: Key words: Adrenal cortex ; Renin-angiotensin system ; Steroidogenesis ; Electron microscopy ; Morphometry ; Rat ; transgenic (mRen2) 27
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Transgenic rats for the murine Ren-2 gene display high blood pressure, low circulating levels of angiotensin II, and high renin content in the adrenal glands. Moreover, transgenic rats possess an increased aldosterone secretion (maximal from 6 to 18 weeks of age), paralleling the development of hypertension. To investigate further the cytophysiology of the adrenal glands of this strain of rats, we performed a combined morphometric and functional study of the zona glomerulosa of 10-week-old female transgenic rats. Morphometry did not reveal notable differences between zona glomerulosa cells of transgenic and age- and sex-matched Sprague-Dawley rats, with the exception of a marked accumulation of lipid droplets, in which cholesterol and cholesterol esters are stored. The volume of the lipid-droplet compartment underwent a significant decrease when transgenic rats were previously injected with angiotensin II or ACTH. Dispersed zona glomerulosa cells of transgenic rats showed a significantly higher basal aldosterone secretion, but their response to angiotensin II and ACTH was similar to that of Sprague-Dawley animals. Angiotensin II-receptor number and affinity were not dissimilar in zona glomerulosa cells of transgenic and Sprague-Dawley rats. These data suggest that the sustained stimulation of the adrenal renin-angiotensin system in transgenic animals causes an increase in the accumulation in zona glomerulosa cells of cholesterol available for steroidogenesis, as indicated by the expanded volume of the lipid-droplet compartment and the elevated basal steroidogenesis. However, the basal hyperfunction of the zona glomerulosa in transgenic animals does not appear to be coupled with an enhanced responsivity to its main secretagogues, at least in terms of aldosterone secretion.
    Type of Medium: Electronic Resource
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  • 19
    ISSN: 1573-2576
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been proposed that angiotensinogen is an acute phase protein, because its plasma concentrations increase during some forms of acute inflammation. However, this is not a consistent finding. Furthermore, no specific function of circulating angiotensinogen in the inflammatory reaction is known. This may be different for extrahepatic synthesis of angiotensinogen, as the local generation of angiotensin II has been implicated in inflammation-related processes in some organs. We have therefore examined the expression of the angiotensinogen gene in liver and extrahepatic tissues under the influence of experimental inflammatory stimuli in comparison to the effects of dexamethasone. Dexamethasone (7 mg/kg intraperitoneally) induced a several-fold increase in angiotensinogen mRNA in liver, aorta, heart, adrenal, and a moderate increase in kidney, testis, and brain. Plasma concentrations of angiotensinogen,α 1,-acid glycoprotein, andα 2-macroglobulin increased, whereas albumin concentrations decreased. Lipopolysaccharide (500 μ/kg subcutaneously) stimulated angiotensinogen mRNA in hepatic, cardiac, renal, adrenal, and testicular tissues, but not in the brain. Plasma concentrations of angiotensinogen,α 1,-acid glycoprotein, andα 2-macroglobulin increased, those of albumin decreased. In turpentine-treated rats (5 ml/kg subcutaneously), angiotensinogen mRNA was reduced in liver and kidney; stimulated in adrenals, testis, and heart; and not influenced in the brain. Plasma concentiations of the acute phase proteins increased, whereas angiotensinogen and albumn decreased. It is concluded that hepatic and extrahepatic angiotensinogen gene expression seem to be regulated similarly by dexamethason and lipopolysaccharide. The different response to turpentine may reflect differences in the pattern of cytokines induced by turpentine or be associated with additional pharmacological effects of turpentine or its metabolites.
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  • 20
    ISSN: 1435-1803
    Keywords: Key words Adrenal – aldosterone – hypertension – renin-angiotensin system – stroke
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have shown that short-term high salt intake unmasks blunted plasma aldosterone suppression in stroke-prone spontaneously hypertensive rats (SHRsp). The aim of this study was to evaluate the response of aldosterone biosynthesis and production to a sustained exposure to the stroke-permissive Japanese-style diet (JD) in young stroke-prone and stroke-resistant SHRs. For this purpose, 6-week old male rats from both strains were divided into 2 dietary groups and received regular diet (SHR = 37, SHRsp = 32) or the JD and 1% saline to drink (SHR = 34, SHRsp = 30) for 4 weeks. All measurements were carried out at the end of the dietary periods. After JD, plasma aldosterone levels were significantly decreased in SHR (from 357.8±57 to 163.3±31.5 pg/ml, p 〈 0.05) but markedly increased in SHRsp (from 442±56.5 to 739±125.7 pg/ml, p 〈 0.05). Consistently, the adrenal aldosterone synthase expression was reduced by JD in SHR (p 〈 0.05), whereas it was even slightly raised by JD in SHRsp so that, at the end of JD, aldosterone synthase mRNA was 5-fold higher in SHRsp than in SHR. Urinary sodium excretion (mEq/24h) achieved lower levels in SHRsp, so that fractional excretion of sodium was 80.2±9% in SHR and 40.3±8% in SHRsp (p 〈 0.05) in balance studies performed at the end of JD. These different responses of mineralocorticoid biosynthesis and urinary sodium excretion to JD were not accounted for by different adaptions of the renin-angiotensin and atrial natriuretic peptide systems, of serum potassium levels, or of adrenal 11β-hydroxylase expression in the two strains. Systolic blood pressure was comparable in both strains throughout the experiment. These results demonstrate enhanced aldosterone biosynthesis, associated with reduced urinary excretion of sodium in response to JD in SHRsp before the onset of stroke. This abnormality may play a role in the higher susceptibility of stroke of this model.
    Type of Medium: Electronic Resource
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