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
Language English Country Switzerland Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22487948
DOI
10.1159/000336823
PII: 000336823
Knihovny.cz E-resources
- MeSH
- Survival Analysis MeSH
- Endothelin A Receptor Antagonists * MeSH
- Atrasentan MeSH
- Angiotensin II Type 1 Receptor Blockers pharmacology MeSH
- Renal Insufficiency, Chronic drug therapy mortality pathology MeSH
- Indoles pharmacology MeSH
- Angiotensin-Converting Enzyme Inhibitors pharmacology MeSH
- Drug Therapy, Combination MeSH
- Rats MeSH
- Kidney pathology MeSH
- Losartan pharmacology MeSH
- Disease Models, Animal MeSH
- Nephrectomy methods MeSH
- Rats, Sprague-Dawley MeSH
- Rats, Transgenic MeSH
- Pyrrolidines pharmacology MeSH
- Receptor, Angiotensin, Type 1 metabolism MeSH
- Receptor, Endothelin A metabolism MeSH
- Hypertension, Renal drug therapy mortality pathology MeSH
- Renin-Angiotensin System drug effects physiology MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Endothelin A Receptor Antagonists * MeSH
- Atrasentan MeSH
- Angiotensin II Type 1 Receptor Blockers MeSH
- Indoles MeSH
- Angiotensin-Converting Enzyme Inhibitors MeSH
- Losartan MeSH
- Pyrrolidines MeSH
- Receptor, Angiotensin, Type 1 MeSH
- Receptor, Endothelin A MeSH
- trandolapril MeSH Browser
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.
References provided by Crossref.org
Altered Balance between Vasoconstrictor and Vasodilator Systems in Experimental Hypertension
