OBJECTIVE: We evaluated the effects of salt restriction and of increasing dietary salt loading on blood pressure and the renin-angiotensin system in transgenic rats with inducible hypertension. METHODS: Hypertension was induced in Cyp1a1-Ren-2 rats through dietary administration of the natural xenobiotic indole-3-carbinol (0.3%), which activates the renin gene. Rats were fed either a normal-salt diet (0.6% NaCl), three different high-salt diets (2, 4 and 8% NaCl) or a low-salt diet (<0.04% NaCl). Blood pressure was monitored by radiotelemetry. Angiotensin II (ANG II) levels were determined by radioimmunoassay. RESULTS: Induction of the renin gene by administration of indole-3-carbinol resulted in normal-salt diet fed animals in the development of severe hypertension that was accompanied by marked increases in plasma and kidney ANG II levels. Feeding the low-salt diet substantially attenuated the development of hypertension. Treatment with the 2 and 4% high-salt diet did not worsen the course of hypertension and did not alter ANG II levels when compared with rats on the normal salt diet. Feeding the 8% high-salt diet exacerbated the course of hypertension and was associated with further strong increases in plasma and kidney ANG II levels. CONCLUSION: Our results demonstrate that after induction of the renin gene in Cyp1a1-Ren-2 transgenic rats inappropriate increases in plasma and kidney ANG II levels in response to very high dietary salt intake are responsible for the development of severe hypertension in this model of inducible renin transgenic rats.

• MeSH
• aldosteron krev   MeSH
• angiotensin II krev   metabolismus   MeSH
• cytochrom P-450 CYP1A1 genetika   metabolismus   MeSH
• hypertenze metabolismus   patofyziologie   MeSH
• kreatinin moč   MeSH
• krevní tlak MeSH
• krysa rodu rattus MeSH
• kuchyňská sůl aplikace a dávkování   MeSH
• ledviny metabolismus   MeSH
• potkani transgenní MeSH
• renin genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The effects of the human renin inhibitor aliskiren on blood pressure (BP), end-organ damage, proteinuria, and tissue and plasma angiotensin (ANG) II levels in young and adult heterozygous Ren-2 transgenic rats (TGR) were evaluated and compared with the effect of the ANG type 1 (AT(1)) receptor blocker losartan during treatment and after 12 days after the withdrawal of drug treatments. BP was monitored by telemetry from the age of 32 days on (young rats) and at 100 days (adult rats). Aliskiren (10 mg·kg(-1)·day(-1) in osmotic minipumps) or losartan (5 mg·kg(-1)·day(-1) in drinking water) treatment was applied for 28 days in young rats and for 70 days in adult rats. In young untreated TGR, severe hypertension rapidly evolved. Adult untreated TGR exhibited stable established hypertension. Both aliskiren and losartan fully prevented the development of hypertension and cardiac hypertrophy in young TGR and normalized BP and cardiac hypertrophy in adult TGR. After cessation of aliskiren treatment in both young and adult TGR BP and cardiac hypertrophy were persistently reduced, while after losartan withdrawal BP and cardiac hypertrophy rapidly increased. In adult aliskiren-treated rats proteinuria was significantly reduced compared with losartan (the effect persisting after withdrawal of treatment), and this decrease strongly correlated with normalization of glomerular size in these animals. In conclusion, aliskiren and losartan had similar antihypertensive effects during chronic treatment, but the antihypertensive and organoprotective effects of aliskiren were persistent even after the 12-day washout period. The durable effect on proteinuria can possibly be attributed to the normalization of glomerular morphology.

• MeSH
• amidy farmakologie   MeSH
• angiotensin II krev   MeSH
• antihypertenziva farmakologie   MeSH
• časové faktory MeSH
• fumaráty farmakologie   MeSH
• glomerulus účinky léků   metabolismus   patologie   MeSH
• hypertenze prevence a kontrola   MeSH
• kardiomegalie prevence a kontrola   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• losartan farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• potkani transgenní MeSH
• proteinurie patologie   prevence a kontrola   MeSH
• renin genetika   metabolismus   MeSH
• srdeční frekvence účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Results of our previous studies have suggested that enhanced generation of superoxide (O2(-)) may contribute to the pathophysiology of hypertension in Ren-2 transgenic rats (TGR). The present study was performed to evaluate in TGR the effects of chronic treatment with the O2(-) scavenger tempol and the antioxidant apocynin on the development of hypertension. Systolic blood pressure (SBP) was monitored from 30 to 99 days of age in TGR and in normotensive Hannover Sprague-Dawley (HanSD) rats. At the end of the experiment, urinary protein and 8-isoprostane excretion were determined and angiotensin II (ANG II) and malondialdehyde (MDA) levels were measured in kidney and cardiac tissues. Cardiac hypertrophy was assessed as the ratio of left heart ventricle weight to tibia length (LVW/TL). Although tempol and apocynin treatment in TGR significantly decreased 8-isoprostane excretion and MAD tissue concentrations as compared with untreated TGR, it did not alter the course of SBP, LVW/TL ratio, proteinuria or ANG II levels that were enhanced as compared with HanSD rats. Our data suggest that the development of hypertension in TGR is clearly ANG II-dependent but the contribution of oxidative stress to the development of hypertension in this model appears to be negligible.

• MeSH
• acetofenony farmakologie   MeSH
• analýza rozptylu MeSH
• angiotensin II analýza   fyziologie   krev   moč   MeSH
• antioxidancia farmakologie   MeSH
• časové faktory MeSH
• cyklické N-oxidy farmakologie   MeSH
• dinoprost analogy a deriváty   moč   MeSH
• hypertenze komplikace   patofyziologie   prevence a kontrola   MeSH
• kardiomegalie komplikace   prevence a kontrola   MeSH
• krevní tlak MeSH
• krysa rodu rattus MeSH
• ledviny chemie   MeSH
• malondialdehyd analýza   MeSH
• modely nemocí na zvířatech MeSH
• myokard chemie   MeSH
• náhodné rozdělení MeSH
• nemoci ledvin komplikace   prevence a kontrola   MeSH
• oxidační stres fyziologie   MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• proteinurie MeSH
• renin genetika   MeSH
• scavengery volných radikálů farmakologie   MeSH
• spinové značení MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

OBJECTIVE: The present study was performed to characterize the autoregulatory efficiency of renal blood flow and glomerular filtration rate and the pressure-natriuresis relationship in transgenic rats with inducible angiotensin II (ANG II)-dependent hypertension (Cyp1a1-Ren-2 rats). METHODS: The renin gene was induced in Cyp1a1-Ren-2 rats through dietary administration of the natural xenobiotic indole-3-carbinol (I3C, 0.3%) for 12 and 24 h, respectively. Noninduced rats served as controls. Anesthetized rats were prepared for renal function studies and an aortic clamp was placed above the junction of the left renal artery to regulate the level of renal arterial pressure. Plasma renin activity, ANG II and aldosterone levels were measured at the end of the experiment by radioimmunoassay. RESULTS: Administration of I3C resulted in progressive increases in plasma renin activity and plasma and kidney ANG II levels; however, it did not significantly alter aldosterone levels as compared with those in noninduced rats. I3C induction for 12 h did not cause significant changes in blood pressure as compared with those in noninduced rats. I3C induction for 24 h elicited a significant rise in blood pressure. Twelve-hour I3C induction caused an impairment of the autoregulatory efficiency of renal blood flow and glomerular filtration rate and of the pressure-natriuresis relationship as compared with that in noninduced rats. In addition, 24 h I3C induction of the renin gene resulted in a marked reduction in renal blood flow and glomerular filtration rate and a further impairment of the pressure-natriuresis mechanism as compared with that in noninduced rats. CONCLUSION: Our findings indicate that an impairment of the pressure-natriuresis mechanism precedes the development of ANG II-dependent hypertension in Cyp1a1-Ren-2 transgenic rats.

• MeSH
• aldosteron krev   MeSH
• angiotensin II metabolismus   MeSH
• blokátory receptoru 1 pro angiotenzin II farmakologie   MeSH
• časové faktory MeSH
• cytochrom P-450 CYP1A1 genetika   MeSH
• hemodynamika účinky léků   MeSH
• hodnoty glomerulární filtrace účinky léků   MeSH
• homeostáza MeSH
• hypertenze genetika   patofyziologie   MeSH
• indoly aplikace a dávkování   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• ledviny krevní zásobení   účinky léků   MeSH
• losartan farmakologie   MeSH
• natriuréza MeSH
• potkani transgenní MeSH
• receptor angiotensinu typ 1 metabolismus   MeSH
• renální oběh účinky léků   MeSH
• renin-angiotensin systém fyziologie   MeSH
• renin genetika   MeSH
• sodík metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

OBJECTIVE: Recent studies have shown that the heptapeptide angiotensin-(1-7) [Ang-(1-7)] exerts important vasoactive actions and can act as an endogenous physiological antagonist of angiotensin II (Ang II) within the renin-angiotensin system (RAS). The present study was performed to evaluate the effects, first, of chronic increases of Ang-(1-7) levels, second, of [7-D-Ala], an Ang-(1-7) receptor antagonist, and, third, of an angiotensin-converting enzyme 2 (ACE2) inhibitor on the course of hypertension and of renal function of the nonclipped kidney in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats. METHODS: Blood pressure (BP) was monitored by radiotelemetry. Elevation of the effect of circulating Ang-(1-7) levels was achieved either by chronic subcutaneous infusion of Ang-(1-7) through osmotic minipumps or by employing transgenic rats that express an Ang-(1-7)-producing fusion protein [Ang-(1-7)TGR+/+] (and its control Ang-(1-7)TGR-/-). [7-D-Ala] was also infused subcutaneously and the ACE2 inhibitor was administrated in drinking water. On day 25 after clipping, rats were anesthetized and renal function was evaluated. RESULTS: Chronic infusion of Ang-(1-7) did not modify the course of 2K1C hypertension and did not alter renal function as compared with saline vehicle-infused 2K1C rats. Chronic infusion of [7-D-Ala] or treatment with the ACE2 inhibitor worsened the course of hypertension and elicited decreases in renal hemodynamics. [Ang-(1-7)TGR+/+] and [Ang-(1-7)TGR-/-] rats exhibited a similar course of hypertension. CONCLUSION: The present data support the notion that Ang-(1-7) serves as an important endogenous vasodilator and natriuretic agent and its deficiency might contribute to the acceleration of 2K1C Goldblatt hypertension.

• MeSH
• angiotensin I farmakologie   genetika   krev   MeSH
• angiotensin II analogy a deriváty   farmakologie   genetika   krev   metabolismus   MeSH
• chirurgické nástroje MeSH
• implantabilní infuzní pumpy MeSH
• kardiomegalie metabolismus   patofyziologie   MeSH
• krevní tlak fyziologie   účinky léků   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• peptidové fragmenty farmakologie   genetika   krev   MeSH
• potkani transgenní MeSH
• progrese nemoci MeSH
• renovaskulární hypertenze chemicky indukované   metabolismus   patofyziologie   MeSH
• telemetrie MeSH
• vazodilatancia farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

OBJECTIVE: The present study was performed to examine in two-kidney, one-clip (2K1C) Goldblatt hypertensive mice: first, the relative contribution of angiotensin II receptor subtypes 1A (AT(1A)) and 1B (AT(1B)); second, the role of angiotensin II type 2 (AT(2)) receptors in the development of hypertension in wild-type (AT(1A)+/+) and AT(1A) receptor knockout (AT(1A)-/-) mice; and third, the role of increased nitric oxide synthase activity in counteracting the hypertensinogenic action of angiotensin II in this model. METHODS: AT(1A)+/+ and AT(1A)-/- mice underwent clipping of one renal artery and were infused with either saline vehicle or selective AT(2) receptor agonist CGP-42112A (CGP). Blood pressure was monitored by radiotelemetry. Blood pressure responses to the nitric oxide synthase inhibitor nitro-L-arginine-methyl-ester were evaluated. RESULTS: AT(1A)+/+ mice responded to clipping by a rise in blood pressure that was not modified by CGP infusion. Clip placement caused a slight increase in blood pressure in AT(1A)-/- mice that remained significantly lower than in AT(1A)+/+ mice. Acute nitric oxide synthase inhibition caused greater increase in blood pressure in 2K1C/AT(1A)+/+ than in AT(1A)+/+ mice. CONCLUSION: The present data support the critical role of AT(1A) receptors in the development of 2K1C hypertension, whereas AT(1B) receptors play only a minor role in blood pressure regulation in this model of angiotensin II-dependent hypertension. Activation of AT(2) receptors does not play an antagonistic role in the AT(1) receptor-mediated hypertensinogenic actions of angiotensin II in this model. Finally, enhanced nitric oxide synthase activity plays a protective role by counteracting the vasoconstrictor influences of angiotensin II in 2K1C hypertensive mice.

• MeSH
• arteria renalis MeSH
• financování organizované MeSH
• hypertenze genetika   patofyziologie   MeSH
• ligace MeSH
• modely nemocí na zvířatech MeSH
• myši knockoutované MeSH
• myši MeSH
• receptor angiotensinu typ 1 fyziologie   genetika   MeSH
• receptor angiotensinu typ 2 fyziologie   genetika   MeSH
• renin-angiotensin systém fyziologie   MeSH
• synthasa oxidu dusnatého fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH

• Publikační typ
• abstrakty MeSH

BACKGROUND: In the present study we evaluated plasma and kidney angiotensin II (ANG II) levels in female and male Ren-2 transgenic rats (TGR) in comparison to age-matched female and male normotensive Hannover Sprague-Dawley rats. METHODS: The rats were maintained on a normal sodium (NS) diet (0.6% NaCl) or fed a high sodium (HS) diet (2% NaCl) for 4 days or were sodium depleted by administration of 40 mg furosemide per liter drinking water overnight followed by 3 days of low sodium diet (0.01% NaCl) (LS + F). ANG II levels were determined by radioimmunoassay. RESULTS: Female TGR at the age of 38 days were already hypertensive and had developed cardiac hypertrophy, whereas male TGR at this age still exhibited a normotensive phenotype. HS diet increased the blood pressure (BP) but did not alter the ANG II levels in TGR at any age. LS + F decreased the BP without significant change in ANG II concentrations in TGR. Female TGR responded to salt loading and salt depletion by more pronounced changes in BP than male TGR. CONCLUSIONS: Female TGR develop hypertension more rapidly and the salt-sensitive component of hypertension is more pronounced in female than in male TGR. Copyright 2007 S. Karger AG, Basel.

• MeSH
• angiotensin II farmakologie   krev   metabolismus   MeSH
• financování organizované MeSH
• geneticky modifikovaná zvířata MeSH
• heterozygot MeSH
• kardiomegalie dietoterapie   krev   MeSH
• krevní tlak MeSH
• krysa rodu rattus MeSH
• kuchyňská sůl terapeutické užití   MeSH
• ledviny krevní zásobení   patofyziologie   MeSH
• pohlavní dimorfismus MeSH
• potkani Sprague-Dawley MeSH
• renální hypertenze dietoterapie   krev   MeSH
• renin-angiotensin systém fyziologie   MeSH
• renin genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH

The aim of the present study was to evaluate the effects of inhibition of cytochrome P-450 (CYP) activity by 1-aminobenzotriazole (ABT) and by CoCl(2), first, on the development of hypertension when treatment was started in young male heterozygous Ren-2 transgenic rats (TGR) and, second, on blood pressure (BP) when treatment was started in adult TGR with established hypertension. Normotensive Hannover Sprague-Dawley (HanSD) rats served as controls. In addition, the renal cortical activities of omega-hydroxylase, the enzyme catalyzing the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), and of epoxygenase, the enzyme responsible for epoxyeicosatrienoic acids (EETs) production, and urinary excretion of 20-HETE and EETs in TGR and HanSD rats were assessed. TGR have higher renal tissue omega-hydroxylase activity and urinary excretion of 20-HETE but have significantly lower renal epoxygenase activity and urinary excretion of EETs than HanSD rats. Treatment of young TGR with ABT and CoCl(2) attenuated the development of hypertension and cardiac hypertrophy and prevented glomerulosclerosis. Administration of ABT and CoCl(2) in adult TGR decreased BP, cardiac hypertrophy, but did not reduce glomerulosclerosis. Our data suggest that altered production and/or action of CYP-derived metabolites play a permissive role in the development and maintenance of hypertension in TGR by enhancing ANG II-induced vasoconstriction.

• MeSH
• cytochrom P450 CYP4A metabolismus   MeSH
• financování organizované MeSH
• fokálně segmentální glomeruloskleróza patofyziologie   MeSH
• heterozygot MeSH
• hypertenze patofyziologie   MeSH
• inhibitory cytochromu P450 MeSH
• inhibitory enzymů farmakologie   MeSH
• kardiomegalie patofyziologie   MeSH
• kobalt MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• kůra ledviny MeSH
• kyseliny hydroxyeikosatetraenové biosyntéza   MeSH
• modely nemocí na zvířatech MeSH
• náhodné rozdělení MeSH
• oxygenasy metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• renin-angiotensin systém fyziologie   MeSH
• renin genetika   metabolismus   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• triazoly farmakologie   MeSH
• vazokonstrikce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

BACKGROUND: The present study was performed in hypertensive Ren-2 transgenic rats (TGR) and in normotensive Hannover Sprague-Dawley (HanSD) rats. First, the intrarenal protein expression of CYP4A, the enzyme catalyzing the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), and of CYP2C23, the enzyme responsible for epoxyeicosatrienoic acid (EET) production, was evaluated. Second, the renal functional responses to inhibition of the intrarenal formation of 20-HETE and EETs were investigated. METHODS: Renal hemodynamics and electrolyte excretion were evaluated in response to the administration of inhibitors of 20-HETE and EET formation into the renal artery. In renal cortical tissue, CYP4A and CYP2C23 protein expression was assessed by Western blot analysis. Urinary concentrations of 20-HETE and EETs were measured using a fluorescent HPLC assay. RESULTS: TGR have higher kidney CYP4A protein expression and urinary 20-HETE excretion but significantly lower CYP2C23 protein expression and urinary EET excretion than HanSD. Intrarenal inhibition of 20-HETE and EET formation decreased sodium excretion in HanSD, whereas inhibition of 20-HETE increased urinary excretion of sodium in TGR without altering renal hemodynamics. CONCLUSIONS: Our data suggest that in TGR, deficient intrarenal synthesis of EETs combined with increased synthesis of 20-HETE with its stimulation of tubular sodium absorption may contribute to the development of hypertension in TGR. 2007 S. Karger AG, Basel

• MeSH
• financování organizované MeSH
• geneticky modifikovaná zvířata MeSH
• hypertenze genetika   patofyziologie   MeSH
• krevní tlak genetika   MeSH
• krysa rodu rattus MeSH
• kyseliny arachidonové fyziologie   MeSH
• kyseliny hydroxyeikosatetraenové fyziologie   MeSH
• ledviny fyziologie   MeSH
• potkani Sprague-Dawley MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH