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

摘要

class="enumerated" style="list-style-type:decimal">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).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 B2-receptor antagonist, HOE140.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).Following 30 min ischaemia in the control group, the creatine kinase activity increased from 0.4 to 53.4 U l⁻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 l⁻¹). This beneficial effect of captopril was completely abolished by the kinin B2-receptor antagonist, HOE140, as well as by the kallidin antiserum.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.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.These data show that captopril increases kallidin-like peptide in the effluent. Kallidin-like peptide via kinin B2 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.