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(Hypertension. 2006;48:572.)
© 2006 American Heart Association, Inc.

Original Articles

Enalapril Attenuates Downregulation of Angiotensin-Converting Enzyme 2 in the Late Phase of Ventricular Dysfunction in Myocardial Infarcted Rat

María Paz Ocaranza; Ivan Godoy; Jorge E. Jalil; Manuel Varas; Patricia Collantes; Melissa Pinto; Maritza Roman; Cristián Ramirez; Miguel Copaja; Guillermo Diaz-Araya; Pablo Castro; Sergio Lavandero

From the Departamento Enfermedades Cardiovasculares, Escuela de Medicina (M.P.O., I.G., J.E.J., M.V., M.P., M.R., C.R., P.C.), P. Universidad Católica de Chile; Instituto de Química (M.V., M.P.), P. Universidad Católica de Valparaiso; Facultad Ciencias Químicas y Farmacéuticas (P.C., M.R., M.C., G.D.-A., S.L.); and Centro FONDAP Estudios Moleculares de la Célula (G.D.-A., S.L.), Facultad de Medicina, Universidad de Chile, Santiago, Chile.

Correspondence to María Paz Ocaranza, PhD, Departamento Enfermedades Cardiovasculares, Escuela de Medicina, P. Universidad Católica de Chile. Marcoleta 391, Santiago, Chile. E-mail mocaran{at}med.puc.cl

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.

Key Words: angiotensin-converting enzyme • myocardial infarction • renin-angiotensin system • remodeling • cardiac function

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