Effects of 17‐beta‐estradiol on cardiac remodeling in the DOCA‐salt model of hypertension

Abstract

Gender differences in cardiovascular disease suggest that estrogens provide cardioprotective effects. Recent clinical trials, however, appear to dispute this hypothesis. We have recently reported that angiotensin-(1–7) (Ang-(1–7)), the product of angiotensin converting enzyme 2 (ACE2) cleavage of angiotensin II, can attenuate aspects of cardiac remodeling in the deoxycorticosterone acetate (DOCA)-salt model of mineralocorticoid hypertension, and others have reported that estrogens increase circulating and tissue levels of ACE2 and Ang-(1–7) in rodents. Here we investigated the effects of chronic 17-beta-estradiol (E2, the most prominent endogenous estrogen) treatment on cardiac remodeling during DOCA-salt hypertension. Female SD rats were ovari- and uninephrectomized, and a 40 mg pellet of DOCA was implanted subcutaneously. Half of these animals also received a subcutaneous 0.1 mg pellet of E2 and DOCA groups were maintained on 0.9% NaCL. DOCA treatment, with or without estrogen, significantly increased blood pressure and ventricular mass. Interstitial fibrosis doubled with DOCA treatment, and this effect was normalized by E2 co-treatment. Together with our previous studies, we conclude that E2 modulates DOCA-induced cardiac fibrosis, and hypothesize that these effects may be mediated through modulation of the ACE2 / Ang-(1–7) axis.