Department of Medical Physiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Can J Physiol Pharmacol. 2019 Jul;97(7):638-646. doi: 10.1139/cjpp-2019-0078. Epub 2019 Mar 6.
Myocardial infarction is a major cause of cardiac dysfunction. All components of the cardiac renin-angiotensin system (RAS) are upregulated in myocardial infarction. 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 (85 mg/kg) to induce AMI. Rats with AMI confirmed biochemically and by ECG, were either left untreated (AMI) or administered DIZE (AMI + DIZE) or enalapril (AMI + enalapril) daily for 4 weeks. DIZE caused a significant activation of cardiac ACE2 compared with 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 mass to total body mass 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.
心肌梗死是心脏功能障碍的主要原因。心肌梗死后，心脏肾素-血管紧张素系统（RAS）的所有成分都上调。血管紧张素转换酶（ACE）和 ACE2 是参与 RAS 成分合成的关键酶，为 RAS 提供了一种代偿机制。我们比较了 ACE2 激活剂地美佐辛（DIZE）与 ACE 抑制剂依那普利对大鼠急性心肌梗死后（AMI）心室功能障碍的心脏保护作用。成年雄性大鼠接受皮下注射生理盐水（对照）或异丙肾上腺素（85mg/kg）以诱导 AMI。通过生物化学和心电图证实患有 AMI 的大鼠，要么未接受治疗（AMI），要么接受 DIZE（AMI+DIZE）或依那普利（AMI+enalapril）治疗，每天一次，持续 4 周。与依那普利相比，DIZE 可显著激活心脏 ACE2。DIZE 显著增强了心脏血液动力学。DIZE 还可降低心脏型脂肪酸结合蛋白（H-FABP）、β-肌球蛋白重链（β-MYH）和心脏质量与总体质量比。这些结果表明，DIZE 通过激活心脏 ACE2 增强了 RAS 的保护轴，并改善了 AMI 后的心肌功能，而依那普利不足以将所有心脏参数恢复正常。
