Institute for Health and Sport, Victoria University, Melbourne, Australia.
Australian Institute for Musculoskeletal Science (AIMSS), University of Melbourne and Western Health, St Albans, Australia.
Clin Exp Pharmacol Physiol. 2020 May;47(5):751-758. doi: 10.1111/1440-1681.13251. Epub 2020 Jan 28.
The renin angiotensin system (RAS) regulates fluid balance, blood pressure and maintains vascular tone. The potent vasoconstrictor angiotensin II (Ang II) produced by angiotensin-converting enzyme (ACE) comprises the classical RAS. The non-classical RAS involves the conversion of Ang II via ACE2 into the vasodilator Ang (1-7) to counterbalance the effects of Ang II. Furthermore, ACE2 converts AngA into another vasodilator named alamandine. The over activation of the classical RAS (increased vasoconstriction) and depletion of the non-classical RAS (decreased vasodilation) results in vascular dysfunction. Vascular dysfunction is the leading cause of atherosclerosis and cardiovascular disease (CVD). Additionally, local RAS is expressed in various tissues and regulates cellular functions. RAS dysregulation is involved in other several diseases such as inflammation, renal dysfunction and even cancer growth. An approach in restoring vascular dysfunction and other pathological diseases is to either increase the activity of ACE2 or reduce the effect of the classical RAS by counterbalancing Ang II effects. The antitrypanosomal agent, diminazene aceturate (DIZE), is one approach in activating ACE2. DIZE has been shown to exert beneficial effects in CVD experimental models of hypertension, myocardial infarction, type 1 diabetes and atherosclerosis. Thus, this review focuses on DIZE and its effect in several tissues such as blood vessels, cardiac, renal, immune and cancer cells.
肾素-血管紧张素系统（RAS）调节体液平衡、血压并维持血管张力。血管紧张素转换酶（ACE）产生的强效血管收缩素血管紧张素 II（Ang II）构成了经典的 RAS。非经典的 RAS 涉及通过 ACE2 将 Ang II 转化为血管扩张素 Ang（1-7），以平衡 Ang II 的作用。此外，ACE2 将 AngA 转化为另一种血管扩张素，命名为 alamandine。经典 RAS 的过度激活（血管收缩增加）和非经典 RAS 的耗竭（血管舒张减少）导致血管功能障碍。血管功能障碍是动脉粥样硬化和心血管疾病（CVD）的主要原因。此外，局部 RAS 在各种组织中表达并调节细胞功能。RAS 失调与其他几种疾病有关，如炎症、肾功能障碍甚至癌症生长。恢复血管功能障碍和其他病理疾病的一种方法是增加 ACE2 的活性或通过平衡 Ang II 的作用来减少经典 RAS 的作用。抗锥虫药物，乙酰苯肼（DIZE），是一种激活 ACE2 的方法。研究表明，DIZE 在高血压、心肌梗死、1 型糖尿病和动脉粥样硬化等 CVD 实验模型中具有有益作用。因此，本综述重点介绍 DIZE 及其在血管、心脏、肾脏、免疫和癌细胞等几种组织中的作用。
