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
Jazyk angličtina Země Švýcarsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
22487948
DOI
10.1159/000336823
PII: 000336823
Knihovny.cz E-zdroje
- MeSH
- analýza přežití MeSH
- antagonisté endotelinového receptoru A * MeSH
- atrasentan MeSH
- blokátory receptoru 1 pro angiotenzin II farmakologie MeSH
- chronická renální insuficience farmakoterapie mortalita patologie MeSH
- indoly farmakologie MeSH
- inhibitory ACE farmakologie MeSH
- kombinovaná farmakoterapie MeSH
- krysa rodu Rattus MeSH
- ledviny patologie MeSH
- losartan farmakologie MeSH
- modely nemocí na zvířatech MeSH
- nefrektomie metody MeSH
- potkani Sprague-Dawley MeSH
- potkani transgenní MeSH
- pyrrolidiny farmakologie MeSH
- receptor angiotensinu typ 1 metabolismus MeSH
- receptor endotelinu A metabolismus MeSH
- renální hypertenze farmakoterapie mortalita patologie MeSH
- renin-angiotensin systém účinky léků fyziologie MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antagonisté endotelinového receptoru A * MeSH
- atrasentan MeSH
- blokátory receptoru 1 pro angiotenzin II MeSH
- indoly MeSH
- inhibitory ACE MeSH
- losartan MeSH
- pyrrolidiny MeSH
- receptor angiotensinu typ 1 MeSH
- receptor endotelinu A MeSH
- trandolapril MeSH Prohlížeč
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.
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