Ferrari R, Cargnoni A, Curello S, Ceconi C, Boraso A, Visioli O
Chair of Cardiology, University of Brescia, Italy.
J Cardiovasc Pharmacol. 1992;20(5):694-704.
We assessed whether local inhibition of myocardial converting enzyme by captopril and zofenopril reduces the functional and metabolic damage caused by ischemia and reperfusion. First we investigated the effects of zofenopril and captopril on the mechanical function, cellular redox state, and norepinephrine (NE) content of isolated and aerobically perfused rabbit hearts. Both drugs failed to modify the myocardial redox state. At concentrations > 10(-6) M, zofenopril, but not captopril, caused a reduction in myocardial NE content. At 10(-4) M, both drugs caused a reduction in developed pressure and an increase in diastolic pressure and release of creatine phosphokinase (CPK). Second we investigated their effects on ischemic and reperfused myocardium. Both drugs exerted a cardioprotection; zofenopril was always more potent than captopril. Recovery of developed pressure on reperfusion improved, and peak release of NE was reduced, as was release of CPK. Calcium homeostasis and mitochondrial function were maintained. Captopril had no effect on occurrence of oxidative stress during reperfusion, whereas zofenopril reduced it. In hearts treated with the converting enzyme inhibitors, peak release of NE was correlated to mitochondrial calcium content, production of ATP, and recovery of mechanical function on reperfusion. These data suggest that the cardioprotective effect of zofenopril and captopril is independent of hemodynamic changes or reduction of the toxicity of oxygen free radicals and that it could be related to a reduction in release of NE.
我们评估了卡托普利和佐芬普利对心肌转化酶的局部抑制作用是否能减轻缺血再灌注所致的功能和代谢损伤。首先，我们研究了佐芬普利和卡托普利对离体且有氧灌注兔心脏的机械功能、细胞氧化还原状态及去甲肾上腺素（NE）含量的影响。两种药物均未能改变心肌氧化还原状态。浓度>10(-6) M时，佐芬普利可使心肌NE含量降低，而卡托普利无此作用。在10(-4) M时，两种药物均使心脏收缩压降低、舒张压升高，并使肌酸磷酸激酶（CPK）释放增加。其次，我们研究了它们对缺血再灌注心肌的影响。两种药物均发挥了心脏保护作用；佐芬普利的作用总是比卡托普利更强。再灌注时心脏收缩压的恢复得到改善，NE的峰值释放减少，CPK释放也减少。钙稳态和线粒体功能得以维持。卡托普利对再灌注期间氧化应激的发生无影响，而佐芬普利可减轻氧化应激。在用转化酶抑制剂处理的心脏中，NE的峰值释放与线粒体钙含量、ATP生成及再灌注时机械功能的恢复相关。这些数据表明，佐芬普利和卡托普利的心脏保护作用独立于血流动力学变化或氧自由基毒性的降低，且可能与NE释放减少有关。
