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Cardioprotective effect of Angiotensin-Converting Enzyme 2 and Angiotensin II type 2 Receptor over-expression in ischemia reperfusion injury in diabetic rats

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

Abstract
Background: Major components of the renin-angiotensin system (RAS) 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: 72 male albino rats 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: Angiotensin Converting Enzyme Inhibitor (ACEI)- protected diabetic rats. At the end of 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 of the heart was determined by the systolic pressure, the diastolic pressure, the heart rate and the peak rate of maximum left ventricular pressure rise (dp/dt). 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 (HOMA IR) 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 DM 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.

Key words: Diabetes, cardiac ischemia reperfusion, ACE2, AT2R expression.


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