Comparison 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


ÖZHAN O. , PARLAKPINAR H. , Acet A.

FUNDAMENTAL & CLINICAL PHARMACOLOGY, 2020 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası:
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1111/fcp.12599
  • Dergi Adı: FUNDAMENTAL & CLINICAL PHARMACOLOGY

Özet

Myocardial ischemia may occur as a result of pathophysiological and therapeutical applications such as atherosclerosis, thromboembolism, percutaneous transluminal coronary angioplasty, coronary artery bypass, and transplantation. In this study, we aimed to compare the effects of angiotensin (Ang) II type 2 (AT(2)) selective receptor agonist Compound 21 (C21), MAS receptor agonist AVE 0991, Ang II type 1 (AT(1)) selective receptor blocker losartan, and Ang-converting enzyme inhibitor captopril on haemodynamic parameters and infarct size on myocardial ischemia/reperfusion (MI/R)-induced necrosis in rats. To induce necrosis in the heart of rats, reperfusion for 2 h following ischemia for 30 min to the descending branch of the left main coronary artery was achieved. C21 (0.03 mg/kg), AVE 0991 (576 mu g/kg), losartan (2 mg/kg), and captopril (3 mg/kg) were administered as an intravenous infusion at 10 min before and throughout the ischemia. Then, the infarct size and risk area were calculated from the heart. The percentage of myocardial infarct size to area at risk ratio (%IS/AR) of groups was Control (MI/R) group: 48.9 +/- 8.8%; C21 group: 31.1 +/- 7.8%; AVE 0991 group: 29.9 +/- 4.8%; C21 + AVE 0991 group: 28.2 +/- 3.3%; Losartan + AVE 0991 group: 30.8 +/- 5.8%; Captopril + AVE 0991 group: 31.7 +/- 7.7%. %IS/AR of the drug-treated groups decreased significantly when compared to the MI/R group (P < 0.05). Our results indicate that the importance of AT(1), AT(2), and MAS receptors in the MI/R injury. Inhibition of Ang II formation by captopril, blockade of AT(1)receptor with losartan, and stimulation of AT(2)receptor with C21 and MAS receptor with AVE 0991 showed beneficial effects by reducing infarct size.