Hypertension Unit, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
J Cardiovasc Pharmacol. 2012 Jan;59(1):58-65. doi: 10.1097/FJC.0b013e3182354776.
Activation of renin-angiotensin system has been linked to cardiovascular and autonomic dysfunctions in diabetes. Experiments were performed to investigate the effects of angiotensin-converting enzyme inhibitor (ACEI), enalapril, on cardiac and autonomic functions in diabetic rats. Diabetes was induced by streptozotocin (50 mg/kg), and rats were treated with enalapril (1 mg · kg(-1) · d(-1)). After 30 days, evaluations were performed in control, diabetic, and enalapril-treated groups. Cardiac function was evaluated by echocardiography and through cannulation of the left ventricle (at baseline and in response to volume overload). Heart rate and systolic blood pressure variabilities were evaluated in the time and frequency domains. Streptozotocin rats had left ventricular systolic and diastolic dysfunctions, expressed by reduced ejection fraction and increased isovolumic relaxation time. The ACEI prevented these changes, improved diastolic cardiac responses to volume overload and total power of heart rate variability, reduced the ACE1 activity and protein expression and cardiac angiotensin (Ang) II levels, and increased angiotensin-converting enzyme 2 activity, despite unchanged blood pressure. Correlations were obtained between Ang II content with systolic and diastolic functions and heart rate variability. These findings provide evidence that the low-dose ACEI prevents autonomic and cardiac dysfunctions induced by diabetes without changing blood pressure and associated with reduced cardiac Ang II and increased angiotensin-converting enzyme 2 activity.
肾素-血管紧张素系统的激活与糖尿病中的心血管和自主神经功能障碍有关。进行实验以研究血管紧张素转换酶抑制剂（ACEI）依那普利对糖尿病大鼠心脏和自主神经功能的影响。通过链脲佐菌素（50mg/kg）诱导糖尿病，并用依那普利（1mg·kg（-1）·d（-1））治疗大鼠。30 天后，在对照组、糖尿病组和依那普利治疗组中进行评估。通过超声心动图和左心室插管（在基线和对容量超负荷的反应中）评估心脏功能。在时间和频率域中评估心率和收缩压变异性。链脲佐菌素大鼠的左心室收缩和舒张功能障碍，表现为射血分数降低和等容舒张时间延长。ACEI 可预防这些变化，改善舒张期心脏对容量超负荷和心率变异性总功率的反应，降低 ACE1 活性和蛋白表达以及心脏血管紧张素（Ang）II 水平，并增加血管紧张素转换酶 2 活性，尽管血压未改变。Ang II 含量与收缩和舒张功能以及心率变异性之间存在相关性。这些发现提供了证据表明，低剂量 ACEI 可预防糖尿病引起的自主和心脏功能障碍，而不改变血压，并与降低心脏 Ang II 和增加血管紧张素转换酶 2 活性有关。
