OBJECTIVE: Evaluation of the effect of endothelin type A (ET A ) receptor blockade on the course of volume-overload heart failure in rats with angiotensin II-dependent hypertension. METHODS: Ren-2 renin transgenic rats (TGR) were used as a model of hypertension. Heart failure was induced by creating an aorto-caval fistula (ACF). Selective ET A receptor blockade was achieved by atrasentan. For comparison, other rat groups received trandolapril, an angiotensin-converting enzyme inhibitor (ACEi). Animals first underwent ACF creation and 2 weeks later the treatment with atrasentan or trandolapril, alone or combined, was applied; the follow-up period was 20 weeks. RESULTS: Eighteen days after creating ACF, untreated TGR began to die, and none was alive by day 79. Both atrasentan and trandolapril treatment improved the survival rate, ultimately to 56% (18 of 31 animals) and 69% (22 of 32 animals), respectively. Combined ACEi and ET A receptor blockade improved the final survival rate to 52% (17 of 33 animals). The effects of the three treatment regimens on the survival rate did not significantly differ. All three treatment regimens suppressed the development of cardiac hypertrophy and lung congestion, decreased left ventricle (LV) end-diastolic volume and LV end-diastolic pressure, and improved LV systolic contractility in ACF TGR as compared with their untreated counterparts. CONCLUSION: The treatment with ET A receptor antagonist delays the onset of decompensation of volume-overload heart failure and improves the survival rate in hypertensive TGR with ACF-induced heart failure. However, the addition of ET A receptor blockade did not enhance the beneficial effects beyond those obtained with standard treatment with ACEi alone.

• MeSH
• angiotensin II MeSH
• atrasentan MeSH
• endotelin-1 MeSH
• endoteliny MeSH
• hypertenze * komplikace   farmakoterapie   MeSH
• inhibitory ACE farmakologie   MeSH
• krysa rodu Rattus MeSH
• píštěle * MeSH
• potkani transgenní MeSH
• receptor angiotensinu typ 1 MeSH
• receptor endotelinu A MeSH
• srdeční selhání * farmakoterapie   etiologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• angiotensin II MeSH
• atrasentan MeSH
• endotelin-1 MeSH
• endoteliny MeSH
• inhibitory ACE MeSH
• receptor angiotensinu typ 1 MeSH
• receptor endotelinu A MeSH