Abstract 326: Angiotensin II Overexpression in the Heart: Effect on Cardiac Function and Remodeling in Deoxycorticosterone Acetate-Salt Hypertension
Angiotensin II (Ang II) has been implicated in cardiac remodeling independent of its hemodynamic effect. Using mice with cardiac-specific expression of a transgene fusion protein that releases Ang II without involvement of the renin-angiotensin system (Tg-Ang II), we tested the hypothesis that increased Ang II in the heart acts locally via the AT1 receptor to exacerbate cardiac hypertrophy and fibrosis in renin-independent hypertension. Male Tg-Ang II mice and their wild-type littermates (WT) were uninephrectomized and divided into
vehicle (tap water);
deoxycorticosterone acetate-salt (DOCA, 10 mg/10 g BW, sc. plus 1% NaCl + 0.2% KCl in drinking water); and
DOCA-salt + angiotensin receptor blocker (ARB, valsartan, 50 mg/kg/day via gavage) for 8 weeks.
Systolic blood pressure (SBP) was measured weekly by tail cuff, and LV ejection fraction (EF) was evaluated by echocardiography. Myocyte cross-sectional area (MCSA) and interstitial collagen fraction (ICF) were studied by morphometric analysis. As shown in the table⇓, DOCA-salt increased SBP to a similar extent in both strains, and this increase was not affected by ARB. However, MCSA and ICF were greater in Tg-Ang II treated with DOCA-salt compared to WT. The anti-hypertrophic and anti-fibrotic responses to ARB were also greater in Tg-Ang mice than WT. EF was similar among groups. DOCA-salt decreased plasma renin concentration (PRC) and ARB significantly increased PRC in both strains. We concluded that
locally produced Ang II worsens cardiac hypertrophy and fibrosis in DOCA-Salt hypertension via activation of AT1 receptors, and
this effect is independent of hemodynamic changes.