Efeects of angiotensin-converting enzyme inhibitor captopril and angiotensin II receptor blockers (AT1, AT2) on myocardial ischemia-reperfusion necrosis in in vivo rat

7.SUMMARY EFFECTS OF ANGIOTENSIN-CONVERTING ENZYME INHIBITOR CAPTOPRIL AND ANGIOTENSIN H RECEPTOR BLOCKERS (ATi, AT2) ON MYOCARDIAL ISCHEMIA-REPERFUSION NECROSIS IN IN VIVO RAT BACKGROUND: Myocardial ischemia-reperfusion (MI-R) represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. Angiotensin II (Ang II) elicits several pathophysiological effects that exacerbate ischemia-reperfusion (I-R) injury. The cardioprotective efficacy of strategies that decrease Ang II production and receptor's stimulation has been investigated in models of I-R injury. The aim of this study was to examine the effects of ACE inhibitor captopril, ATi and AT2 receptor blockers, losartan and PD 123 3 19, on ischemia- reperfusion induced myocardial infarct size in an in vivo rat model. MATERIAL AND METHODS: To produce necrosis, a branch of the descending left coronary artery was occluded for 30 min followed by two hours reperfusion. ECG changes, blood pressure and heart rate were measured during all experiment. Captopril (3mg/kg), losartan (2mg/kg) and PD123319 (20ug/kg/min) were given IV. 10 min before ischemia and continued during ischemia. Infarction was measured triphenyl tetrazolium staining. The volume of infarct and the risk zone was determined by planimetry. RESULTS: Compared to the control group [%55. 62+4.00] both captopril and losartan significantly reduced myocardial infarct size [%30.50±3.26 and %37.75+4.44] whereas neither PD123319 nor PD123319+losartan did not affect infarct size [46.50±3.72 and 54.62±2.43J. CONCLUSION: Our results indicate that, blockage of Ang II produce by captopril or ATi receptor antagonist losartan exert cardioprotective activity after I-R injury. The therapeutic success of these drugs is related to their unique pharmacological profile involving both a reduction of plasma and tissue Ang II concentrations and blockage of Ang II harmful effects by ATi receptor. Also, the infarct size reduction by losartan was abolished with blockade of the AT2 receptor, suggesting a cardioprotective action of losartan through a signal cascade of AT2 receptor activation, bradykinin and prostaglandins. Key Words: Angiotensin n, captopril, losartan, AT2 receptor, myocardial ischemia- reperfusion, necrosis. 71