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

Abstract

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 (AT2) selective receptor agonist Compound 21 (C21), MAS receptor agonist AVE 0991, Ang II type 1 (AT1) 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 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. 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 AT1, AT2, and MAS receptors in the 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 infarct size.

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

“…Angiotensin II, through the angiotensin II type 1 receptor—a G‐protein‐coupled receptor—triggers the retention of sodium and consequently the water, the vasoconstriction, and aldosterone secretion with mineralocorticoid receptor engagement [6]. The activation of mineralocorticoid receptors and angiotensin II type 1 receptor at heart and vessel level has been reported to promote endothelial dysfunction and cardiac remodeling [3,6,7]. Angiotensin II, activating angiotensin II type 2 receptors, counteracts most of the activities triggered via angiotensin II type 2 receptors [7].…”

“…The activation of mineralocorticoid receptors and angiotensin II type 1 receptor at heart and vessel level has been reported to promote endothelial dysfunction and cardiac remodeling [3,6,7]. Angiotensin II, activating angiotensin II type 2 receptors, counteracts most of the activities triggered via angiotensin II type 2 receptors [7].…”

“…More recently, new components of the renin‐angiotensin system have been characterized [7–10]. There are new enzymes, such as (i) angiotensin‐converting enzyme‐2 which can catalyze the conversion of angiotensin II to angiotensin 1–7 [Ang‐(1–7)], or (ii) neutral endopeptidase and prolyl endopeptidase which convert angiotensin I to angiotensin 1–7, and (iii) neutral endopeptidase and angiotensin‐converting enzyme which can convert the angiotensin 1–9 [Ang‐(1–9)], the angiotensin I‐metabolite, to [Ang‐(1–7)] [9].…”

“…In complement to the beneficial cardiovascular effects of activating angiotensin II type 2 receptors, the angiotensin‐converting enzyme 2/[Ang‐(1–7)]/Mas axis opposes most of the action of the classical ACE/angiotensin II/angiotensin II type 1 receptor axis [7].…”

“…In their study, Ozhan et al [7] aimed to examine the effects of different treatments compared to the control group—such as (i) an angiotensin‐converting enzyme inhibitor, captopril, (ii) an angiotensin II type 1 receptor blocker, losartan, (iii) an angiotensin II type 2 selective receptor agonist, the compound 21 (C21), and (iv) a nonpeptide Ang‐(1–7) Mas receptor agonist, AVE 0991—on myocardial ischemia‐reperfusion (MI/R)‐induced infarct size in the rat animal model.…”