Coutinho Danielle C O, Monnerat-Cahli Gustavo, Ferreira Anderson J, Medei Emiliano
Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antônio Carlos, 6627-31.270-901, Belo Horizonte, MG, Brazil.
Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Ilha do Fundão, 21.949-000, Rio de Janeiro, Brazil.
Europace. 2014 Nov;16(11):1689-96. doi: 10.1093/europace/euu070. Epub 2014 Apr 15.
Diabetic patients present a high level of cardiac arrhythmias and risk of cardiac sudden death. The renin-angiotensin system (RAS) plays a key role in diabetes and cardiac diseases. The present study aimed to evaluate whether an angiotensin-converting enzyme 2 (ACE2) activator, diminazene aceturate (DIZE), could improve the streptozotocin (STZ)-induced electrical changes in ventricular repolarization in hyperglycaemic rats.
Hyperglycaemia was induced in Wistar male rats with STZ (60 mg/kg/iv). After 4 weeks of STZ injection, rats were daily treated with saline (control) or DIZE (1 mg/kg/gavage) for four consecutive weeks. The cardiac electrical function was evaluated in vivo by electrocardiogram and in vitro by cardiac action potential records in different pacing frequencies. Treatment with DIZE was not able to reverse hyperglycaemia nor body weight loss. However, DIZE reversed hyperglycaemia-induced cardiac electrical changes in ventricular repolarization. Specifically, animals treated with DIZE showed shorter QT and QTc intervals. In addition, ACE2 activation was capable to shorten the cardiac action potential and also reverse the arrhythmic markers. Diminazene aceturate treatment did not induce arrhythmic events in normal, as well as in hyperglycaemic animals.
Our data indicate that activation of ACE2 has a beneficial effect in hyperglycaemic rats, improving the cardiac electrical function. Thus, DIZE represents a promising new therapeutic agent to treat hyperglycaemia-induced cardiac electrical changes in ventricular repolarization.
糖尿病患者存在高水平的心律失常和心脏性猝死风险。肾素 - 血管紧张素系统（RAS）在糖尿病和心脏疾病中起关键作用。本研究旨在评估血管紧张素转换酶2（ACE2）激活剂乙酰氨基阿维菌素（DIZE）是否能改善链脲佐菌素（STZ）诱导的高血糖大鼠心室复极的电变化。
用STZ（60 mg/kg静脉注射）诱导Wistar雄性大鼠高血糖。在注射STZ 4周后，大鼠连续4周每天接受生理盐水（对照）或DIZE（1 mg/kg灌胃）治疗。通过心电图在体内评估心脏电功能，并在体外以不同起搏频率记录心脏动作电位来评估。DIZE治疗不能逆转高血糖或体重减轻。然而，DIZE逆转了高血糖诱导的心室复极心脏电变化。具体而言，用DIZE治疗的动物QT和QTc间期缩短。此外，ACE2激活能够缩短心脏动作电位并逆转心律失常标志物。乙酰氨基阿维菌素治疗在正常动物和高血糖动物中均未诱发心律失常事件。
我们的数据表明，ACE2激活对高血糖大鼠有有益作用，可改善心脏电功能。因此，DIZE是一种有前景的新型治疗药物，可用于治疗高血糖诱导的心室复极心脏电变化。
