Abstract 2057: Role of AT2 Receptor in Cardiac Function and Remodeling Post-MI in Mice with Cardiac Overexpression of Angiotensin II
Angiotensin II (Ang II) acting on type 1 receptors (AT1) causes hypertension and cardiac hypertrophy, whereas activation of the AT2 receptor, which stimulates release of kinins and nitric oxide (NO), may have an anti-hypertrophic and cardioprotective effect. We previously showed that overexpression of angiotensin II (Ang II) in the heart (Tg-AngII) caused cardiac hypertrophy and fibrosis and promoted cardiac dysfunction and remodeling post-myocardial infarction (MI) without a hemodynamic effect. Here we studied whether blockade of AT2 enhances the detrimental effect of Ang II in Tg-Ang II mice. Male 12–14-week-old Tg-Ang II mice and their wild-type littermates (WT) were subjected to MI or sham-MI with or without AT2-ant (PD123319 20mg/kg/day i. p. via miniosmotic pump) for 8 weeks. Systolic blood pressure (SBP) was measured by tail cuff. LV ejection fraction (EF) and LV mass were evaluated by echocardiography. Infarct size (IS), myocyte cross-sectional area (MCSA) and interstitial collagen fraction (ICF) were studied histopathologically. We found that SBP was similar between strains and was not influenced by AT2-ant with or without MI. AT2-ant did not affect IS, but significantly increased cardiac rupture and mortality in Tg-Ang II+AT2-ant compared to Tg-Ang II+Veh (73.5% vs 54.7%; p < 0.05) and to WT+AT2-ant (73.5% vs 45.5%, p < 0.01). Cardiac remodeling and dysfunction post-MI were more severe in Tg-Ang II mice and were further worsened by AT2-ant (Table⇓). However, in both strains with sham-MI, AT2-ant had no effect on functional and morphological parameters. We concluded that locally produced Ang II worsens cardiac remodeling and dysfunction post-MI via activation of AT1, whereas AT2 may counteract AT1 and play a cardioprotective role in the heart.