Endothelin receptor blockade improves endothelial function in human internal mammary arteries.
CARDIOVASCULAR RESEARCH(2001)
摘要
Objective: Endothelial dysfunction, specifically endothelium-derived contracting factors have been implicated in the development of arterial conduit vasospasm. The potent vasoconstrictor endothelin-1 (ET-1) has received much attention in this regard. The present study was designed to evaluate the role of ET-I in the development of endothelial dysfunction in human internal mammary arteries (IMA). To this aim, we examined the effects of specific and non-specific ET-receptor antagonists on endothelial function (assessed using acetylcholine (ACh)-induced vasodilation) in segments of IMA obtained during coronary artery bypass graft (CABG) surgery. Methods: Vascular segments of IMA were obtained from 51 patients undergoing elective coronary artery bypass graft (CABG) surgery and in vitro endothelium-dependent and -independent responses to ACh and sodium nitroprusside (SNP) were assessed. Isometric dose response curves (DRC) to ACh and SNP were constructed in pre-contracted rings in the presence and absence of bosentan (ETA/B receptor antagonist, 3 muM), BQ-123 (ETA antagonist, 1 muM) and BQ-788 (ETB antagonist, 1 muM) using the isolated organ bath apparatus. Percent maximum relaxation (%E-max) and sensitivity (pEC(50)) were compared between interventions. Results: ACh caused dose-dependent endothelium-mediated relaxation in IMA (%E-max 43+/-4, pEC(50) 6.74+/-0.12). In the presence of bosentan, BQ-123 and BQ-788 ACh-induced relaxation was significantly augmented (%E-max bosentan 60+/-3, BQ-123 56+/-4, BQ-788 53+/-5 vs. control 43+/-4, P<0.05) without affecting sensitivity. The effects of these antagonists were endothelium-specific since endothelium-independent responses to SNP remained unaltered. Furthermore, the beneficial effects were independently and maximally mediated by ETA and ETB receptors (%E-max BQ-123 56+/-4 vs. BQ-788 53+/-5 vs, bosentan 60+/-3, P>0.05). Conclusions: These data uncover, for the first time, beneficial effects of ET receptor blockade on endothelium-dependent vasorelaxation in human IMA. (C) 2001 Elsevier Science B.V. All rights reserved.
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关键词
endothelial function,endothelins,cardiovascular surgery,vasoactive agents,vasoconstriction/dilation
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