Han H, Neubauer S, Braeker B, Ertl G
Department of Medicine, Würzburg University, Federal Republic of Germany.
J Mol Cell Cardiol. 1995 Feb;27(2):761-6. doi: 10.1016/0022-2828(95)90081-0.
A potential detrimental role of endothelin-1 in myocardial ischemia/reperfusion injury was studied by use of the endothelin-1 antagonists BQ123 and BQ610. Isolated isovolumetric rat hearts were perfused at constant pressure. BQ123 (7 micrograms/min) and BQ610 (1.75 micrograms/min) did not alter mechanical function or coronary flow and shifted dose-response curves for endothelin-1 significantly to the right. In rats subjected to 30 min of no-flow ischemia, the increase of left ventricular resting pressure was significantly delayed by BQ123 and BQ610 compared to control (BQ123: 20 +/- 2* mmHg, BQ610: 19 +/- 2* mmHg, control: 44 +/- 4 mmHg at 15 min of ischemia, respectively, P < 0.05 v control). With reperfusion after 30 min of ischemia, recovery of left ventricular developed pressure was not significantly affected but tended to be better with endothelin-1 antagonist pretreatment (BQ123: 20 +/- 3 mmHg; BQ610: 19 +/- 3 mmHg, control 12 +/- 3 mmHg). However, in hearts subjected to 15 min of ischemia followed by reperfusion, recovery of left ventricular developed pressure was improved by BQ610 pretreatment (BQ610: 52 +/- 8 mmHg, control: 24 +/- 6 mmHg). We conclude: BQ123 and BQ610 effectively antagonize the coronary constrictive effect of endothelin-1. BQ123 and BQ610 delay the development of contracture during ischemia and may improve functional recovery during reperfusion. Our findings suggest that endogenous endothelin-1 may contribute to ischemia/reperfusion injury.
通过使用内皮素 -1拮抗剂BQ123和BQ610，研究了内皮素 -1在心肌缺血/再灌注损伤中的潜在有害作用。将离体的等容大鼠心脏在恒压下灌注。BQ123（7微克/分钟）和BQ610（1.75微克/分钟）不改变机械功能或冠脉血流，并使内皮素 -1的剂量反应曲线显著右移。在经历30分钟无血流缺血的大鼠中，与对照组相比，BQ123和BQ610显著延迟了左心室静息压力的升高（缺血15分钟时，BQ123：20±2* mmHg，BQ610：19±2* mmHg，对照组：44±4 mmHg，P < 0.05 vs对照组）。缺血30分钟后再灌注时，左心室舒张末压的恢复未受到显著影响，但内皮素 -1拮抗剂预处理后有改善的趋势（BQ123：20±3 mmHg；BQ610：19±3 mmHg，对照组12±3 mmHg）。然而，在经历15分钟缺血后再灌注的心脏中，BQ610预处理改善了左心室舒张末压的恢复（BQ610：52±8 mmHg，对照组：24±6 mmHg）。我们得出结论：BQ123和BQ610有效拮抗内皮素 -1的冠脉收缩作用。BQ123和BQ610延迟缺血期间挛缩的发展，并可能改善再灌注期间的功能恢复。我们的研究结果表明内源性内皮素 -1可能促成缺血/再灌注损伤。
