Enalapril attenuates downregulation of Angiotensin-converting enzyme 2 in the late phase of ventricular dysfunction in myocardial infarcted rat.
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.
Ocaranza
María Paz
MP
Departamento Enfermedades Cardiovasculares, Escuela de Medicina, P. Universidad Católica de Chile. mocaran@med.puc.cl
Godoy
Ivan
I
Jalil
Jorge E
JE
Varas
Manuel
M
Collantes
Patricia
P
Pinto
Melissa
M
Roman
Maritza
M
Ramirez
Cristián
C
Copaja
Miguel
M
Diaz-Araya
Guillermo
G
Castro
Pablo
P
Lavandero
Sergio
S
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
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)