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- Title
Effects of Combined Endothelin A Receptor and Renin-Angiotensin System Blockade on the Course of End-Organ Damage in 5/6 Nephrectomized Ren-2 Hypertensive Rats.
- Authors
Vaněčková, Ivana; Kujal, Petr; Husková, Zuzana; Vaňourková, Zdeňka; Vernerová, Zdenka; Čertíková Chábová, Věra; Škaroupková, Petra; Kramer, Herbert J.; Tesař, Vladimír; Červenka, Luděk
- Abstract
Our previous studies in rats with ablation nephrectomy have shown similar cardiorenal protective effects of renin-angiotensin system (RAS)-dependent treatment (combination of angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker) and RAS-independent treatment (combination of α- and β-adrenoreceptor antagonist and diuretics). Moreover, selective blockade of endothelin (ET) receptor type A (ETA) improved survival rate and attenuated hypertension and organ damage in Ren-2 transgenic rats. Therefore, we were interested in whether ETA receptor blockade could have additive effects to the classical blockade of the RAS. Transgenic rats underwent 5/6 renal ablation at the age of 2 months and were treated for 20 weeks with RAS blockers alone (angiotensin II receptor blocker - losartan, and angiotensin-converting enzyme inhibitor - trandolapril), ETA receptor blocker alone (atrasentan) or with the combination of RAS and ETA receptor blockade. RAS blockade normalized blood pressure and improved survival. It decreased cardiac hypertrophy and proteinuria as well as tissue angiotensin II and ET-1 levels. In contrast, ETA receptor blockade only partially improved survival rate, reduced blood pressure, attenuated the development of cardiac hypertrophy and transiently reduced proteinuria. However, no additive cardio- and renoprotective effects of ETA and RAS blockade were noted at the end of the study. Copyright © 2012 S. Karger AG, Basel
- Subjects
RATS; NEPHRECTOMY; RENIN-angiotensin system; ENZYME inhibitors; DIURETICS
- Publication
Kidney & Blood Pressure Research, 2012, Vol 35, Issue 5, p382
- ISSN
1420-4096
- Publication type
Article
- DOI
10.1159/000336823