Comparation of the effects of losartan, captopril, angiotensin ii type 2 receptor agonist compound 21 and MAS receptor agonist ave 0991 on myocardial ischemia-reperfusion necrosis in rats

Aim: Myocardial ischemia may occur as a result of pathophysiological and therapeutic applications such as atherosclerosis, thromboembolism, percutaneous transluminal coronary angioplasty, coronary artery by-pass and transplantation. In this study, we aimed to compare the effects of AT2 selective receptor agonist Compound 21 (C21), MAS receptor agonist AVE 0991, AT1 selective receptor blocker losartan and angiotensin converting enzyme inhibitor captopril on hemodynamic parameters and infarct size on MI/R-induced necrosis in rats. Material and Method: To induce necrosis in the heart of rats, reperfusion for 2 hours following ischemia for 30 minutes to the descending branch of the left main coronary artery was applied. C21 (0.03 mg/kg), AVE 0991 (576 μg/kg), losartan (2 mg/kg) and captopril (3 mg/kg) were administered as an intravenous infusion at 10 min before and throughout the ischemia. The size of the necrosis and risk area was calculated. Results: Necrosis area/risk area ratios of groups were; MI/R: 48.9±8.8%; C21+MI/R: 31.1±7.8%; AVE 0991+MI/R: 29.9±4.8%; C21+AVE 0991+MI/R: 28.2±3.3%; Losartan+AVE 0991+MI/R: 30.8±5.8%; Captopril+AVE 0991+MI/R: 31.7±7.7%. The ratio of necrosis area/risk area of the drug treated groups decreased significantly compared to the MI/R group (p<0.05). Conclusion: Our results indicate that the importance of Ang II receptor subtypes and MAS receptors in MI/R injury. Inhibition of Ang II formation by captopril, blockade of AT1 receptor with losartan and stimulation of AT2 receptor with C21 and MAS receptor with AVE 0991 showed beneficial effects by reducing necrotic area induced by MI/R injury. Key Words: AVE 0991, Compound 21, Captopril, Losartan, Myocardial ischemia-reperfusion injury.