title: Similar renoprotection after renin-angiotensin-dependent and -independent antihypertensive therapy in 5/6-nephrectomized Ren-2 transgenic rats: are there blood pressure-independent effects?
abstract: 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.
authors.affiliation: Department for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Kujal
authors.forename: Věra Čertíková
authors.initials: VČ
authors.lastname: Chábová
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Vernerová
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Walkowska
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kompanowska-Jezierska
authors.forename: Janusz
authors.initials: J
authors.lastname: Sadowski
authors.forename: Zdeňka
authors.initials: Z
authors.lastname: Vaňourková
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Husková
authors.forename: Martin
authors.initials: M
authors.lastname: Opočenský
authors.forename: Petra
authors.initials: P
authors.lastname: Skaroupková
authors.forename: Stanislava
authors.initials: S
authors.lastname: Schejbalová
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Kramer
authors.forename: Dan
authors.initials: D
authors.lastname: Rakušan
authors.forename: Jan
authors.initials: J
authors.lastname: Malý
authors.forename: Ivan
authors.initials: I
authors.lastname: Netuka
authors.forename: Ivana
authors.initials: I
authors.lastname: Vaněčková
authors.forename: Libor
authors.initials: L
authors.lastname: Kopkan
authors.forename: Luděk
authors.initials: L
authors.lastname: Cervenka
mesh_terms: D000450:Aldosterone / Q000652:urine; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D006332:Cardiomegaly / Q000188:drug therapy / Q000517:prevention & control; D003404:Creatinine / Q000097:blood / Q000378:metabolism / Q000652:urine; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000517:prevention & control; D004232:Diuretics / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005665:Furosemide / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D007741:Labetalol / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D011507:Proteinuria / Q000097:blood / Q000378:metabolism / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics; D007211:Indoles; D006852:Hydrochlorothiazide; D000804:Angiotensin II; C052035:trandolapril; D000450:Aldosterone; D005665:Furosemide; D003404:Creatinine; D012083:Renin; D019808:Losartan; D007741:Labetalol