CARDIOPROTECTIVE EFFECT OF ANGIOTENSIN-CO NVERTING ENZYME-INHIBITORS ON MYOCARDIAL ISCHEMIA REPERFUSION INJURY/

After transient episodes of ischemia, benefits of thrombolytic or angi oplastic therapy may be limited by reperfusion injury. Angiotensin-con verting enzyme inhibitors protect the heart against ischemia/reperfusi on injury, an effect mediated by kinins, We examined whether the prote ctive effect of the angiotensin-converting enzyme inhibitor ramiprilat on myocardial ischemia/reperfusion is due to kinin stimulation of pro staglandin and/or nitric oxide release, The left anterior descending c oronary artery of Lewis inbred rats was occluded for 30 minutes, follo wed by 120 minutes of reperfusion, Immediately before reperfusion rats were treated with vehicle, ramiprilat, or the angiotensin II type I r eceptor antagonist losartan, We tested whether pretreatment with the k inin receptor antagonist HOE 140, the nitric oxide synthase inhibitor N-G-nitro-L-arginine methyl ester, or the cyclooxygenase inhibitor ind omethacin blocked the effect of ramiprilat on infarct size and reperfu sion arrhythmias. In controls, infarct size as a percentage of the are a at risk was 79 +/- 3%; ramiprilat reduced this to 49 +/- 4% (p < 0.0 01), but losartan had little effect (74 +/- 6%, p = ns), Pretreatment with HOE 140, N-G-nitro-L-arginine methyl ester, or indomethacin aboli shed the beneficial effect of ramiprilat, Compared with the 30-minute ischemia/120-minute reperfusion group, nonreperfused hearts with 30 mi nutes of ischemia had significantly smaller infarct size as a percenta ge of the area at risk, whereas in the 150-minute ischemia group it wa s significantly larger, This suggests that reperfusion caused a signif icant part of the myocardial injury, but it also suggests that compare d with prolonged ischemia, reperfusion salvaged some of the myocardium , Ventricular arrhythmias mirrored the changes in infarct size, Thus, angiotensin-converting enzyme inhibitors protect the myocardium agains t ischemia/reperfusion injury and arrhythmias; these beneficial effect s are mediated primarily by a kinin-prostaglandin-nitric oxide pathway , not inhibition of angiotensin II formation.