Hagar J M
University of California, Irvine 92714.
Am J Physiol. 1994 Nov;267(5 Pt 2):H1833-41. doi: 10.1152/ajpheart.1994.267.5.H1833.
Endothelin (ET)-1 is produced in response to myocardial ischemia and reperfusion. It is a potent constrictor of coronary resistance vessels and may therefore contribute to myocardial injury and postischemic microvascular dysfunction. Isolated buffer-perfused rabbit hearts, under conditions of constant flow and isovolumic contraction, underwent 60 min of global ischemia and 60 min of reperfusion after pretreatment with selective ETA receptor antagonist BQ-123 (10(-7) M) in perfusate, exogenous ET-1 (10(-11) M), or control. Release of ET increased significantly at 20 and 60 min of reperfusion. BQ-123 did not enhance the recovery of left ventricular developed pressure or coronary perfusion pressure, whereas exogenous ET tended to worsen them. Cumulative creatine kinase release over 20 min of reperfusion did not differ significantly between groups. Maximum endothelium-dependent dilation to acetylcholine (ACh) was initially 62 +/- 6, 71 +/- 6, and 63 +/- 8% (SE) of U-46619-induced preconstriction in control, BQ-123-, and ET-treated hearts. At 20 min of reperfusion it was 37 +/- 5, 73 +/- 9, and 22 +/- 5%, and at 60 min of reperfusion it was 35 +/- 7, 79 +/- 6, and 22 +/- 3% (P < 0.001 for BQ-123 vs. control at 20 min and P < 0.0001 at 60 min). Endothelium-independent dilation to nitroglycerin was unaltered by ischemia and reperfusion. Neither BQ-123 alone nor a 1-h infusion of ET (10(-10) M) altered the response to ACh in nonischemic hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
内皮素（ET）-1是在心肌缺血和再灌注时产生的。它是冠状动脉阻力血管的强效收缩剂，因此可能导致心肌损伤和缺血后微血管功能障碍。在恒流和等容收缩条件下，对离体缓冲灌注兔心进行预处理，分别在灌注液中加入选择性ETA受体拮抗剂BQ-123（10⁻⁷M）、外源性ET-1（10⁻¹¹M）或作为对照，然后进行60分钟的全心缺血和60分钟的再灌注。再灌注20分钟和60分钟时，ET的释放显著增加。BQ-123并未增强左心室舒张末压或冠状动脉灌注压的恢复，而外源性ET则倾向于使其恶化。再灌注20分钟内肌酸激酶的累积释放量在各组之间无显著差异。在对照、BQ-123处理和ET处理的心脏中，对乙酰胆碱（ACh）的最大内皮依赖性舒张最初分别为U-46619诱导的预收缩的62±6%、71±6%和63±8%（标准误）。再灌注20分钟时分别为37±5%、73±9%和22±5%，再灌注60分钟时分别为35±7%、79±6%和22±3%（再灌注20分钟时BQ-123组与对照组相比P<0.001，60分钟时P<0.0001）。对硝酸甘油的非内皮依赖性舒张不受缺血和再灌注的影响。单独使用BQ-123或1小时输注ET（10⁻¹⁰M）均未改变非缺血心脏对ACh的反应。（摘要截短于250字）
