We evaluated the effects of N(G)-nitro-L-arginine methylester (L-NAME) (50 mg/kg/day) and 7-nitroindazole (7NI) (10 mg/kg/day) administered from 10th-16th week of age either individually or together on cardiovascular system of Wistar rats and SHR. Systolic blood pressure (sBP) was measured weekly by the plethysmographic method. For morphological studies, the animals (n=10) were perfused with a fixative (120 mm Hg), and thoracic aorta and carotid and coronary arteries were processed for electron microscopy. For functional investigation (n=10), aortic rings were used in an organ bath. In Wistar rats, L-NAME evoked an increase of sBP; hypertrophy of the heart and arterial walls; an increase in cross-sectional areas (CSA) of endothelial cells (EC), muscle cells (SMC), extracellular matrix (ECM), and a decrease in acetylcholine-induced endothelial-dependent relaxation (EDR). 7NI evoked sBP-independent hypotrophy of the heart and arterial walls, a decrease in CSA of EC and SMC without affecting the CSA of ECM, and a mild decrease in acetylcholine-induced EDR. 7NI and L-NAME administered together evoked lower effect on BP and trophicity of the heart and all arteries, and a similar decrease in acetylcholine-induced EDR compared to L-NAME alone. In SHR, 7NI did not evoke any effect on the studied parameters.

• MeSH
• aorta thoracica účinky léků   enzymologie   patofyziologie   ultrastruktura   MeSH
• arteriae carotides účinky léků   enzymologie   patofyziologie   ultrastruktura   MeSH
• hypertenze farmakoterapie   enzymologie   patologie   patofyziologie   MeSH
• indazoly farmakologie   MeSH
• inhibitory enzymů farmakologie   MeSH
• kardiomegalie enzymologie   patologie   patofyziologie   prevence a kontrola   MeSH
• koronární cévy účinky léků   enzymologie   patofyziologie   ultrastruktura   MeSH
• krevní tlak účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• NG-nitroargininmethylester farmakologie   MeSH
• potkani inbrední SHR MeSH
• potkani Wistar MeSH
• remodelace cév účinky léků   MeSH
• remodelace komor účinky léků   MeSH
• srdeční komory účinky léků   enzymologie   patologie   patofyziologie   MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   metabolismus   MeSH
• vazodilatace účinky léků   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

1. Hypertension plays a critical role in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD), but it has also been postulated that antihypertensive drugs that block the renin-angiotensin system (RAS) show class-specific renoprotective actions beyond their blood pressure (BP)-lowering effects. 2. Because this notion has recently been questioned, in the present study we compared the effects of a RAS-dependent antihypertensive therapy (a combination of trandolapril, an angiotensin-converting enzyme inhibitor (ACEI) and losartan, an angiotensin-II (AngII) receptor subtype 1A receptor antagonist) with a 'RAS-independent' antihypertensive therapy (a combination of labetalol, an alfa- and beta-adrenoreceptor antagonist with the diuretics, hydrochlorothiazide and furosemide) on the progression of CKD after 5/6 renal ablation (5/6 NX) in Ren-2 renin transgenic rats (TGR), a model of AngII-dependent hypertension. Normotensive transgene-negative Hannover Sprague-Dawley (HanSD) rats after 5/6 NX served as controls. 3. RAS-dependent and -independent antihypertensive therapies normalized BP and survival rate, and prevented the development of cardiac hypertrophy and glomerulosclerosis to the same degree in 5/6 NX HanSD rats and in 5/6 NX TGR. The present findings show that renoprotection, at least in rats after 5/6 NX, is predominantly BP-dependent. When equal lowering of BP was achieved, leading to normotension, cardio- and renoprotective effects were equivalent irrespective of the type of antihypertensive therapy. 4. These findings should be taken into consideration in attempts to develop new therapeutic approaches and strategies aimed to prevent the progression of CKD and to lower the incidence of ESRD.

• MeSH
• aldosteron moč   MeSH
• angiotensin II krev   metabolismus   MeSH
• antihypertenziva farmakologie   MeSH
• blokátory receptoru 1 pro angiotenzin II farmakologie   MeSH
• chronické selhání ledvin farmakoterapie   metabolismus   prevence a kontrola   MeSH
• chymosin metabolismus   MeSH
• diabetické nefropatie farmakoterapie   prevence a kontrola   MeSH
• diuretika farmakologie   MeSH
• furosemid farmakologie   MeSH
• hydrochlorthiazid farmakologie   MeSH
• hypertenze farmakoterapie   metabolismus   MeSH
• indoly farmakologie   MeSH
• inhibitory ACE farmakologie   MeSH
• kardiomegalie farmakoterapie   prevence a kontrola   MeSH
• kombinovaná farmakoterapie MeSH
• kreatinin krev   metabolismus   moč   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• labetalol farmakologie   MeSH
• losartan farmakologie   MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• proteinurie krev   metabolismus   moč   MeSH
• renin-angiotensin systém účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus 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

We aimed to compare the effect of angiotensin converting enzyme (ACE) inhibitors captopril (containing thiol group) and enalapril (without thiol group) on the development of spontaneous hypertension and to analyze mechanisms of their actions, particularly effects on oxidative stress and NO production. Six-week-old SHR were divided into three groups: control, group receiving captopril (50 mg/kg/day) or enalapril (50 mg/kg/day) for 6 weeks. At the end of experiment, systolic blood pressure (SBP) increased by 41 % in controls. Both captopril and enalapril prevented blood pressure increase, however, SBP in the captopril group (121+/-5 mmHg) was significantly lower than that in the enalapril group (140+/-5 mmHg). Concentration of conjugated dienes in the aorta was significantly lower in the captopril group compared to the enalapril group. Captopril and enalapril increased NO synthase activity in the heart and aorta to the similar level. Neither captopril nor enalapril was, however, able to increase the expression of eNOS. Both ACE inhibitors increased the level of cGMP. However, cGMP level was significantly higher in the aorta of captopril group. We conclude that captopril, beside inhibition of ACE, prevented hypertension by increasing NO synthase activity and by simultaneous decrease of oxidative stress which resulted in increase of cGMP concentration.

• MeSH
• antihypertenziva farmakologie   terapeutické užití   MeSH
• aorta účinky léků   enzymologie   MeSH
• časové faktory MeSH
• enalapril farmakologie   terapeutické užití   MeSH
• guanosinmonofosfát cyklický metabolismus   MeSH
• hypertenze komplikace   genetika   metabolismus   patofyziologie   prevence a kontrola   MeSH
• inhibitory ACE farmakologie   terapeutické užití   MeSH
• kaptopril farmakologie   terapeutické užití   MeSH
• kardiomegalie etiologie   prevence a kontrola   MeSH
• kardiomyocyty účinky léků   enzymologie   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• oxid dusnatý metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• potkani inbrední SHR MeSH
• sulfhydrylové sloučeniny farmakologie   terapeutické užití   MeSH
• synthasa oxidu dusnatého metabolismus   MeSH
• upregulace 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

• MeSH
• hypoxie MeSH
• inhibitory ACE farmakologie   MeSH
• kardiomegalie etiologie   prevence a kontrola   MeSH
• kolagen MeSH
• krysa rodu rattus MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH

• MeSH
• hypertenze etiologie   prevence a kontrola   MeSH
• kaptopril fyziologie   MeSH
• kardiomegalie etiologie   prevence a kontrola   MeSH
• krysa rodu rattus MeSH
• oxid dusnatý nedostatek   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH