Ocaranza María Paz, Godoy Ivan, Jalil Jorge E, Varas Manuel, Collantes Patricia, Pinto Melissa, Roman Maritza, Ramirez Cristián, Copaja Miguel, Diaz-Araya Guillermo, Castro Pablo, Lavandero Sergio
Departamento Enfermedades Cardiovasculares, Escuela de Medicina, P. Universidad Católica de Chile.
Hypertension. 2006 Oct;48(4):572-8. doi: 10.1161/01.HYP.0000237862.94083.45. Epub 2006 Aug 14.
The early and long-term effects of coronary artery ligation on the plasma and left ventricular angiotensin-converting enzyme (ACE and ACE2) activities, ACE and ACE2 mRNA levels, circulating angiotensin (Ang) levels [Ang I, Ang-(1-7), Ang-(1-9), and Ang II], and cardiac function were evaluated 1 and 8 weeks after experimental myocardial infarction in adult Sprague Dawley rats. Sham-operated rats were used as controls. Coronary artery ligation caused myocardial infarction, hypertrophy, and dysfunction 8 weeks after surgery. At week 1, circulating Ang II and Ang-(1-9) levels as well as left ventricular and plasma ACE and ACE2 activities increased in myocardial-infarcted rats as compared with controls. At 8 weeks post-myocardial infarction, circulating ACE activity, ACE mRNA levels, and Ang II levels remained higher, but plasma and left ventricular ACE2 activities and mRNA levels and circulating levels of Ang-(1-9) were lower than in controls. No changes in plasma Ang-(1-7) levels were observed at any time. Enalapril prevented cardiac hypertrophy and dysfunction as well as the changes in left ventricular ACE, left ventricular and plasmatic ACE2, and circulating levels of Ang II and Ang-(1-9) after 8 weeks postinfarction. Thus, the decrease in ACE2 expression and activity and circulating Ang-(1-9) levels in late ventricular dysfunction post-myocardial infarction were prevented with enalapril. These findings suggest that in this second arm of the renin-angiotensin system, ACE2 may act through Ang-(1-9), rather than Ang-(1-7), as a counterregulator of the first arm, where ACE catalyzes the formation of Ang II.
在成年斯普拉格-道利大鼠实验性心肌梗死后1周和8周，评估冠状动脉结扎对血浆和左心室血管紧张素转换酶（ACE和ACE2）活性、ACE和ACE2 mRNA水平、循环血管紧张素（Ang）水平[Ang I、Ang-(1-7)、Ang-(1-9)和Ang II]以及心脏功能的早期和长期影响。假手术大鼠用作对照。冠状动脉结扎术后8周导致心肌梗死、心肌肥大和心脏功能障碍。在第1周，与对照组相比，心肌梗死大鼠的循环Ang II和Ang-(1-9)水平以及左心室和血浆ACE和ACE2活性增加。心肌梗死后8周，循环ACE活性、ACE mRNA水平和Ang II水平仍较高，但血浆和左心室ACE2活性和mRNA水平以及Ang-(1-9)的循环水平低于对照组。在任何时候均未观察到血浆Ang-(1-7)水平的变化。依那普利可预防梗死后8周时的心肌肥大和心脏功能障碍以及左心室ACE、左心室和血浆ACE2的变化，以及Ang II和Ang-(1-9)的循环水平变化。因此，依那普利可预防心肌梗死后晚期心室功能障碍中ACE2表达和活性以及循环Ang-(1-9)水平的降低。这些发现表明，在肾素-血管紧张素系统的这一第二条途径中，ACE2可能通过Ang-(1-9)而非Ang-(1-7)发挥作用，作为第一条途径（其中ACE催化Ang II的形成）的一种负调节因子。
