Linz W, Schölkens B A
Department of Pharmacology, Hoechst AG, Frankfurt, F.R.G.
J Cardiovasc Pharmacol. 1987;10 Suppl 7:S75-82. doi: 10.1097/00005344-198706107-00012.
To investigate the influence of local cardiac converting enzyme (CE) inhibition on the effects of angiotensin I (ANG I), ANG II, and bradykinin (BK), experiments were performed in ischemic isolated perfused working rat hearts. Acute regional myocardial ischemia was induced by 15 min occlusion of the left coronary artery followed by reperfusion. In ischemic isolated rat hearts, perfusion with ramiprilat (100 ng/ml, 2.58 x 10(-7) mol/l), the active moiety of the CE inhibitor ramipril, after coronary occlusion protected against ventricular fibrillation that invariably occurred in untreated control hearts in the reperfusion period. Addition of ANG I and ANG II to the perfusate enhanced, whereas BK reduced postischemic reperfusion arrhythmias, which were almost abolished in the hearts from ramipril (1 mg/kg p.o.) pretreated rats. Perfusion with ANG I and ANG II reduced cardiac function and coronary flow, increased the activities of lactate dehydrogenase and creatine kinase in the perfusate, and decreased high-energy-rich phosphates and glycogen in the myocardium. In contrast, BK reduced the enzymatic activities in the perfusate and improved the metabolic parameters in the myocardium. In hearts from ramipril pretreated animals, the ANG I effects were abolished, whereas the ANG II actions remained unchanged. The results of these experiments are consistent with the hypothesis that the beneficial effects of CE inhibitors on ventricular arrhythmias, cardiac function, and metabolism are due to local interference with CE in the coronary vascular wall or heart tissue and subsequent reduction of local ANG II generation and BK degradation.
为研究局部心脏转化酶（CE）抑制对血管紧张素I（ANG I）、血管紧张素II（ANG II）和缓激肽（BK）作用的影响，在缺血的离体灌注工作大鼠心脏上进行了实验。通过阻断左冠状动脉15分钟后再灌注诱导急性局部心肌缺血。在缺血的离体大鼠心脏中，冠状动脉闭塞后用雷米普利拉（100 ng/ml，2.58×10⁻⁷ mol/l）灌注，雷米普利是CE抑制剂雷米普利的活性部分，可预防再灌注期未治疗的对照心脏中总是发生的心室颤动。向灌注液中添加ANG I和ANG II可增强缺血后再灌注心律失常，而BK可减少这种心律失常，在口服雷米普利（1 mg/kg）预处理的大鼠心脏中，这种心律失常几乎被消除。用ANG I和ANG II灌注会降低心脏功能和冠状动脉血流量，增加灌注液中乳酸脱氢酶和肌酸激酶的活性，并降低心肌中的高能磷酸盐和糖原。相反，BK可降低灌注液中的酶活性并改善心肌中的代谢参数。在雷米普利预处理动物的心脏中，ANG I的作用被消除，而ANG II的作用保持不变。这些实验结果与以下假设一致，即CE抑制剂对室性心律失常、心脏功能和代谢的有益作用是由于对冠状动脉血管壁或心脏组织中CE的局部干扰以及随后局部ANG II生成和BK降解的减少。
