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Up‐regulation of ACE2 by enalapril is associated to lower cardiac remodeling in myocardial infarcted rat
Author(s) -
Ocaranza María Paz,
Varas Manuel,
Godoy Ivan,
Pinto Melissa,
Román Maritza,
Nilo Flavia,
Mackenzie Denisse,
Alarcón Miguel,
Jalil Jorge,
Lavandero Sergio
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1008-a
The role of ACE2 in cardiac late remodeling post myocardial infarction (MI) remains unexplored. We hypothetized that the up‐regulation of ACE2 levels by enalapril is associated to less left ventricular (LV) hypertrophy and fibrosis in the late phase of LV dysfunction. Sham‐operated (S) or myocardial infarcted (MI) rats were randomized to receive either vehicle or enalapril (ENA, 10 mg/kg BW/day) for 8 wk. Ligation of coronary artery (LCA) induced LV infarction (29% of the LV perimeter), hypertrophy and LV dysfunction. Circulating ACE activity and Ang II levels as well as LV ACE mRNA levels remained significantly higher after 8 wk post‐MI (p<0.05) but plasma and LV ACE2 activities and LV ACE2 mRNA levels were significantly lower than in controls (p<0.05). No changes in plasma bradikinins (BK)‐(1,7), BK‐(1,9) and Ang‐(1–7) levels were observed at any time. ENA prevented LVH, myocardial dysfunction, LV fibrosis, and changes in plasma and LV ACE and ACE2 activities and circulating levels of Ang II. Ang –(1–9) and BK‐(1–9) plasma levels increased significantly with ENA (p<0.05). In summary, the selective decrease in the ACE2 expression and activity in late remodeling post‐MI was prevented with ENA and suggest that ACE2 through Ang‐(1,9) and BK‐(1–9) rather than Ang‐(1–7) may act as a counter‐regulator of the RAS pathway. Fondecyt 1040832