Endothelin-receptor blockade improves endothelial vasomotor dysfunction in heart failure

被引:33
作者
Bauersachs, J
Fraccarollo, D
Galuppo, P
Widder, J
Ertl, G
机构
[1] Univ Wurzburg, Med Klin, D-97080 Wurzburg, Germany
[2] Univ Klinikum Mannheim, Med Klin 2, Mannheim, Germany
[3] Univ Heidelberg, Fak Klin Med Mannheim, Heidelberg, Germany
关键词
endothelial function; endothelins; free radicals; heart failure; nitric oxide; vasoconstriction/dilation;
D O I
10.1016/S0008-6363(00)00083-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives: To elucidate the effect of selective endothelin ETA- and mixed ETA/B-receptor antagonists on endothelial vasomotor dysfunction in rats with heart failure after myocardial infarction (MI). Methods: Vasoreactivity and superoxide anion formation were determined in aortic rings from Wistar rats 12 weeks after extensive MI (>46% of left ventricle) compared to sham-operated animals. Rats were either treated with the selective ETA-receptor antagonist LU 135352 (30 mg/kg/day), the mixed ETA/B-receptor antagonist Bosentan (100 mg/kg/day) or placebo. Results: In MI rats, the concentration-response curve of the endothelium-dependent, nitric oxide-mediated relaxation induced by acetylcholine was significantly shifted to the right and the maximum relaxation was attenuated. Long-term treatment with both ET antagonists significantly improved acetylcholine-induced relaxation in MI rats. LU 135251 was more effective than Bosentan. Endothelium-independent relaxations induced by sodium nitroprusside as well as endothelin- and phenylephrine-induced contractions were similar in all groups of rats. Plasma renin activity and aortic superoxide formation, which were enhanced in rats with heart failure, were normalized by LU 135252, but not by Bosentan treatment. Conclusions: Long-term treatment with ET-receptor antagonists improves endothelial vasomotor dysfunction in rats with chronic MI. This mechanism may essentially contribute to the beneficial effects of ET receptor blockade in heart failure. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:142 / 149
页数:8
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