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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

I. Vaněčková, P. Kujal, Z. Husková, Z. Vaňourková, Z. Vernerová, V. Certíková Chábová, P. Skaroupková, HJ. Kramer, V. Tesař, L. Červenka

. 2012 ; 35 (5) : 382-392.

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc13000886

Grantová podpora
NS10500 MZ0 CEP - Centrální evidence projektů
NS9703 MZ0 CEP - Centrální evidence projektů
NT12171 MZ0 CEP - Centrální evidence projektů

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 (ET(A)) improved survival rate and attenuated hypertension and organ damage in Ren-2 transgenic rats. Therefore, we were interested in whether ET(A) 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), ET(A) receptor blocker alone (atrasentan) or with the combination of RAS and ET(A) 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, ET(A) 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 ET(A) and RAS blockade were noted at the end of the study.

Citace poskytuje Crossref.org

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