THE DELETERIOUS EFFECTS OF EXOGENOUS ANGIOTENSIN-I AND ANGIOTENSIN-IION MYOCARDIAL ISCHEMIA-REPERFUSION INJURY

Angiotensin II is well known to have a cardiotoxic effects. However, i t is still unclear whether exogenous angiotensin I or angiotensin II h as a deleterious effect on myocardial ischemia-reperfusion injury. To examine this deleterious effect, we administered angiotensin I and ang iotensin II to perfused hearts before ischemia, and measured creatine kinase (CK) release and cardiac function during subsequent reperfusion . Wistar Kyoto rats were used and the hearts were perfused by the Lang endorff technique at a constant flow (10 ml/n-tin). Seven hearts were perfused for 20 min and then subjected to 15 min of global ischemia (C ontrol). In the experimental groups, during the 5 min before ischemia, we administered 100 ng /ml angiotensin I (Ang I; n = 9), mug/ml enala prilat (ACEI; n = 5), both agents (ACEI + Ang I) (n = 6), or 10 ng/ml angiotensin II (Ang 11; n=6). The perfusates were then sampled to meas ure angiotensin II. After 15 min of ischemia, the hearts were reperfus ed with control perfusate. Throughout the 20 min of reperfusion, the e ffluent was collected to measure cumulative CK release. Angiotensin I increased coronary perfusion pressure (CPP) by 32 +/- 4 mmHg, however, the angiotension converting enzyme inhibitor inhibited the increase o f CPP by angiotension I (11 +/- 1 mmHg) (p < 0.01). The contents of an giotensin II in the effluent in Ang I and Ang I + ACEI were 11.5 +/- 1 .9 ng/ml and 4.0 +/- 0.5 ng/ml (p<0.01). After 20 min of reperfusion, the left ventricular developed pressure was unchanged in all of the gr oups. CPP was also unchanged by ischemia in all of the groups. Ventric ular fibrillation was occurred only in Ang I and Ang II, with an incid ence of 44% and 33%, respectively. The cumulative CK in Control, Ang 1 , ACEI, Ang I + ACEI, and Ang II was 7 +/- 1 IU, 19 +/- 2 IU,* 7 +/- 1 IU, 12 +/- 1 IU+ and 20 +/- 2* IU. (**; p < 0*01 vs Control. +; p < 0.05 vs Ang I). Angiotensin I (100 ng/ml) and angiotensin II (10 ng/m l) both produced ischemia-reperfusion injuries. Angiotensin I is conve rted to angiotensin II in cardiac tissue, and this angiotensin II is s upposed to have a deleterious effect on ischemia-reperfusion injury. T his harmful effect may not be related to the vasoconstriction induced by angiotensin II.