Schölkens B A, Linz W
Hoechst AG, Frankfurt, (Main), FR Germany.
Clin Exp Hypertens A. 1988;10(6):1259-70. doi: 10.1080/07300077.1988.11878916.
The interaction of the converting enzyme (CE)-inhibitor ramipril and the bradykinin (BK)-antagonist D-Arg-[Hyp2, Thi5,8, D-Phe7]BK with angiotensin I (ANG), ANG II and BK were studied in isolated hearts of rats and guinea pigs. In isolated working rat hearts perfusion with ANG I and ANG II reduced cardiac function and coronary flow, increased the activities of lactate dehydrogenase (LDH) and creatine kinase (CK) in the perfusate, decreased high-energy rich phosphates and glycogen in the myocardium and increased duration and incidence of post-ischemic reperfusion arrhythmias. BK on the other hand reduced LDH and CK activities, improved metabolic parameters in the myocardium and reduced reperfusion arrhythmias. In isolated rat hearts pretreatment with ramipril protected against reperfusion arrhythmias and reduced enzyme activities of LDH and CK in the coronary effluent. Cardiodynamic parameters and coronary flow improved and myocardial tissue levels of glycogen, ATP and creatine phosphate (CP) were elevated. Almost identical changes were seen during perfusion with BK. The cardioprotective effects produced by both, the CE-inhibitor and BK, were completely abolished when the BK-antagonist was added to the perfusate, while a smaller inhibition was obtained by indomethacin perfusion. In isolated guinea pig hearts BK increased coronary flow. Single-dose oral pretreatment with ramipril potentiated, whereas perfusion with the BK-antagonist abolished this effect. These data add support to the hypothesis that local inhibition of CE = kininase II contributes to the beneficial effects of CE-inhibitors in the heart.
在大鼠和豚鼠的离体心脏中，研究了转化酶（CE）抑制剂雷米普利与缓激肽（BK）拮抗剂D-Arg-[Hyp2, Thi5,8, D-Phe7]BK 与血管紧张素I（ANG）、血管紧张素II（ANG II）和BK的相互作用。在离体工作的大鼠心脏中，灌注ANG I和ANG II会降低心脏功能和冠脉流量，增加灌注液中乳酸脱氢酶（LDH）和肌酸激酶（CK）的活性，降低心肌中的高能磷酸盐和糖原含量，并增加缺血后再灌注心律失常的持续时间和发生率。另一方面，BK可降低LDH和CK活性，改善心肌代谢参数并减少再灌注心律失常。在离体大鼠心脏中，用雷米普利预处理可预防再灌注心律失常，并降低冠脉流出液中LDH和CK的酶活性。心脏动力学参数和冠脉流量得到改善，心肌组织中的糖原、ATP和磷酸肌酸（CP）水平升高。在灌注BK期间也观察到几乎相同的变化。当向灌注液中加入BK拮抗剂时，CE抑制剂和BK产生的心脏保护作用均被完全消除，而通过吲哚美辛灌注可获得较小程度的抑制作用。在离体豚鼠心脏中，BK可增加冠脉流量。单剂量口服雷米普利预处理可增强这种作用，而灌注BK拮抗剂则可消除这种作用。这些数据支持了以下假说，即局部抑制CE = 激肽酶II有助于CE抑制剂在心脏中发挥有益作用。
