title: Enalapril attenuates downregulation of Angiotensin-converting enzyme 2 in the late phase of ventricular dysfunction in myocardial infarcted rat.
abstract: 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.
authors.affiliation: Departamento Enfermedades Cardiovasculares, Escuela de Medicina, P. Universidad Católica de Chile. mocaran@med.puc.cl
authors.forename: María Paz
authors.initials: MP
authors.lastname: Ocaranza
authors.forename: Ivan
authors.initials: I
authors.lastname: Godoy
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Jalil
authors.forename: Manuel
authors.initials: M
authors.lastname: Varas
authors.forename: Patricia
authors.initials: P
authors.lastname: Collantes
authors.forename: Melissa
authors.initials: M
authors.lastname: Pinto
authors.forename: Maritza
authors.initials: M
authors.lastname: Roman
authors.forename: Cristián
authors.initials: C
authors.lastname: Ramirez
authors.forename: Miguel
authors.initials: M
authors.lastname: Copaja
authors.forename: Guillermo
authors.initials: G
authors.lastname: Diaz-Araya
authors.forename: Pablo
authors.initials: P
authors.lastname: Castro
authors.forename: Sergio
authors.initials: S
authors.lastname: Lavandero
mesh_terms: D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015536:Down-Regulation; D004656:Enalapril / Q000494:pharmacology*; D006439:Hemodynamics; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D010446:Peptide Fragments / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018754:Ventricular Dysfunction / Q000201:enzymology*; D016277:Ventricular Function, Left
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D010446:Peptide Fragments; C506331:angiotensin I (1-9); D000804:Angiotensin II; D004656:Enalapril; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)