Kallidin-like peptide mediates the cardioprotective effect of the ACE inhibitor captopril against ischaemic reperfusion injury of rat heart

摘要

1 The potential cardioprotective effect of ACE inhibitors has been attributed to the inhibition of bradykinin degradation. Recent data in rats documented a kallidin-like peptide, which mimics the cardioprotective effect of ischaemic preconditioning. This study investigates in isolated Langendorff rat heart the effect of the ACE inhibitor captopril, the role of bradykinin, kallidin-like peptide, and nitric oxide (NO). 2 The bradykinin level in the effluent of the control group was 14.6 pg ml~(-1) and was not affected by captopril in the presence or absence of kinin B_2-receptor antagonist, HOE 140. 3 The kallidin-like peptide levels were approximately six-fold higher (89.8 pg ml~(-1)) and increased significantly by treatment with captopril (144 pg ml~(-1)), and simultaneous treatment with captopril and HOE140 (197 pg ml~(-1)). 4 Following 30 min ischaemia in the control group, the creatine kinase activity increased from 0.4 to 53.4 U 1~(-1). In the captopril group and in the captopril + L-NAME group, the creatine kinase activity was significantly lower (18.5 and 22.8 U 1~(-1)). This beneficial effect of captopril was completely abolished by the kinin B_2-receptor antagonist, HOE140, as well as by the kallidin antiserum. 5 Perfusion of the hearts with kallidin before the 30 min ischaemia, but not with bradykinin, yielded an approximately 50% reduction in creatine kinase activity after reperfusion. 6 Pretreatment with L-NAME alone and simultaneously with captopril, and with kallidin, respectively, suggests a kinin-independent action of NO before the 30 min ischaemia on coronary flow and a kinin-dependent action after ischaemia. 7 These data show that captopril increases kallidin-like peptide in the effluent. Kallidin-like peptide via kinin B_2 receptor seems to be the physiological mediator of cardioprotective actions of captopril against ischaemic reperfusion injury. HOE140 as well as the kallidin antiserum abolished the cardioprotective effects of captopril.