The deleterious effects of exogenous angiotensin I and angiotensin II on myocardial ischemia-reperfusion injury.
Angiotensin II is well known to have a cardiotoxic effects. However, it is still unclear whether exogenous angiotensin I or angiotensin II has a deleterious effect on myocardial ischemia-reperfusion injury. To examine this deleterious effects, we administered angiotensin I and angiotensin 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 Langendorff technique at a constant flow (10 ml/min). Seven hearts were perfused for 20 min and then subjected to 15 min of global ischemia (Control). In the experimental groups, during the 5 min before ischemia, we administered 100 ng/ml angiotensin I (Ang I; n = 9), 1 microgram/ml enalaprilat (ACEI; n = 5), both agents (ACEI + Ang I) (n = 6), or 10 ng/ml angiotensin II (Ang II; n = 6). The perfusates were then sampled to measure angiotensin II. After 15 min of ischemia, the hearts were reperfused with control perfusate. Throughout the 20 min of reperfusion, the effluent 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 of CPP by angiotension I (11 +/- 1 mmHg) (p < 0.01). The contents of angiotensin 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 groups. CPP was also unchanged by ischemia in all of the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
First Department of Internal Medicine, Osaka City University Medical School, Japan.
M
M
Yoshiyama
S
S
Kim
H
H
Yamagishi
T
T
Omura
T
T
Tani
M
M
Takagi
I
I
Toda
M
M
Teragaki
K
K
Akioka
K
K
Takeuchi
D000803:Angiotensin I / Q000633:toxicity*; D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D003326:Coronary Circulation; D003402:Creatine Kinase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000502:physiology
D000804:Angiotensin II; D000803:Angiotensin I; D003402:Creatine Kinase