Could cardioprotective effect of ACE2 activator "diminazene aceturate" is more potent than ACE inhibitor "Enalapril" on acute myocardial infarction in rats?

Myocardial infarction (MI) is a major cause of cardiac dysfunction. All components of the cardiac renin angiotensin system (RAS) are upregulated in MI. Angiotensin converting enzyme (ACE) and ACE2 are key enzymes involved in synthesis of components of RAS and provide a counter-regulatory mechanism within RAS. We compared the cardioprotective effect of the ACE2 activator diminazene aceturate (DIZE) versus the ACE inhibitor (enalapril) on post acute myocardial infarction (AMI) ventricular dysfunction in rats. Adult male rats received subcutaneous injections of either saline (control) or isoproterenol (ISO) (85 mg/kg) to induce AMI. Rats with AMI confirmed biochemically and by ECG, were either left untreated (AMI) or administered diminazene (AMI +DIZE), or enalapril (AMI +enalapril) daily for 4 weeks. DIZE caused a significant activation of cardiac ACE2 compared to enalapril. DIZE caused a significantly greater enhancement of cardiac hemodynamics. DIZE also caused greater reductions in heart-type fatty acid binding protein (H-FABP), β-myosin heavy chain (β-MYH), and in heart weight/total body weight ratio. These results indicated that activation of cardiac ACE2 by DIZE enhanced the protective axis of RAS and improved myocardial function following AMI, whereas enalapril was not sufficient to restore all cardiac parameters back to normal.