Cardioprotective eff ect of angiotensin-converting enzyme 2 and angiotensin II Type 2 receptor over-expression in ischemia reperfusion injury in diabetic rats

Abstract

Maha M. Sabry, Nagwa K. Roshdy, Hany E. ElSebaee, Laila A. Rashed, Mary A. Youssef, Amal F. Tawadrous

Background: Major components of the renin-angiotensin system such as angiotensin II (Ang II), angiotensin converting enzyme (ACE), ACE2, Ang II Type 1 receptors (AT1R) and Ang II Type 2 receptors (AT2R) have been identified in human and rodent heart cells. Over-activation of this system has been reported to play a key role in diabetes. Methods: A total of 72 male albino rats (160-180 g) were divided into the following groups each containing 18 rats. Group 1: Control group, Group 2: Type 2 diabetic control rats, Group 3: Angiotensin receptor blocker (ARB) -protected diabetic rats and Group 4: ACE inhibitor (ACEI) protected diabetic rats. At the end of the experiment, half the number of rats in all groups was sacrificed, and the heart excised and perfused according to the Langendorff technique. Mechanical performance of the left ventricle (LV) of the heart was determined by the systolic pressure, the diastolic pressure, the heart rate and the peak rate of maximum LV pressure rise (dp/dt), which is considered as a good index of contractility. These mechanical performances were monitored during pre-ischemic; ischemic and post-ischemic reperfusion phases. From the other group of rats (n = 9), tissue was extracted from the heart for estimation of AT2R and ACE2 gene expression. Results: Treatment with ARBs and ACEIs significantly lowered blood glucose, insulin levels and homeostasis model assessment insulin resistance index compared to untreated diabetic rats. However, values did not return to control values. ARBs and ACEI improved myocardial performance and percentage recovery following ischemia reperfusion. The cardio protective effect was more pronounced in the ARBs Group. This positively correlated with increased AT2R and ACE2 expression in all studied Groups. However, there was no significant correlation between the level of AT2R and ACE2 expression in cardiac tissue. Conclusion: The use of ARBs and ACEIs in Type 2 diabetes mellitus significantly offered cardio-protection against ischemia-reperfusion injury either through improving the diabetic condition or by increasing the expression of AT2R and/or ACE2 in cardiac tissue.