Document Detail

Similar renoprotection after renin-angiotensin-dependent and -independent antihypertensive therapy in 5/6-nephrectomized Ren-2 transgenic rats: are there blood pressure-independent effects?
MedLine Citation:
PMID:  20880190     Owner:  NLM     Status:  MEDLINE    
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.
Petr Kujal; Věra Čertíková Chábová; Zdenka Vernerová; Agnieszka Walkowska; Elzbieta Kompanowska-Jezierska; Janusz Sadowski; Zdeňka Vaňourková; Zuzana Husková; Martin Opočenský; Petra Skaroupková; Stanislava Schejbalová; Herbert J Kramer; Dan Rakušan; Jan Malý; Ivan Netuka; Ivana Vaněčková; Libor Kopkan; Luděk Cervenka
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  37     ISSN:  1440-1681     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-30     Completed Date:  2011-03-10     Revised Date:  2012-09-17    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  1159-69     Citation Subset:  IM    
Copyright Information:
© 2010 The Authors. Clinical and Experimental Pharmacology and Physiology © 2010 Blackwell Publishing Asia Pty Ltd.
Department for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
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MeSH Terms
Aldosterone / urine
Angiotensin II / blood,  metabolism
Angiotensin II Type 1 Receptor Blockers / pharmacology
Angiotensin-Converting Enzyme Inhibitors / pharmacology
Antihypertensive Agents / pharmacology*
Blood Pressure / drug effects*
Cardiomegaly / drug therapy,  prevention & control
Creatinine / blood,  metabolism,  urine
Diabetic Nephropathies / drug therapy,  prevention & control
Diuretics / pharmacology
Drug Therapy, Combination
Furosemide / pharmacology
Hydrochlorothiazide / pharmacology
Hypertension / drug therapy*,  metabolism
Indoles / pharmacology
Kidney Failure, Chronic / drug therapy,  metabolism,  prevention & control*
Labetalol / pharmacology
Losartan / pharmacology
Proteinuria / blood,  metabolism,  urine
Rats, Sprague-Dawley
Rats, Transgenic
Renin / metabolism
Renin-Angiotensin System / drug effects*
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Diuretics; 0/Indoles; 11128-99-7/Angiotensin II; 114798-26-4/Losartan; 36894-69-6/Labetalol; 52-39-1/Aldosterone; 54-31-9/Furosemide; 58-93-5/Hydrochlorothiazide; 60-27-5/Creatinine; 87679-37-6/trandolapril; EC

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