Abstract P609: Estrogen Receptor ERα Plays a Major Role in Oxidative Stress Dependent Myocardial Dysfunction Caused by Ethanol in Conscious Female Rats
Ethanol elicits estrogen (E2)-dependent myocardial oxidative stress and dysfunction in female rats. The aim of this study was to elucidate the role of the individual E2 receptor (ER), ERα, ERβ, and the G protein-coupled estrogen receptor-1 (GPER), in the ethanol-evoked myocardial dysfunction. To achieve this goal, female rats in proestrus phase (highest E2 level) received selective antagonist (200 μg/kg; i.v) of ERα (MPP), ERβ (PHTPP) or GPER (G15) or saline 30 min before ethanol (1 g/kg; i.v) or saline infusion. ERα blockade virtually abrogated ethanol-evoked myocardial dysfunction and hypotension, while ERβ blockade had no effect on the hypotensive response, but caused delayed attenuation of the ethanol-evoked reductions in left ventricular developed pressure and the rate of left ventricle pressure rise. GPER blockade caused delayed attenuation of both cardiovascular effects of ethanol. While all 3 ERs subtype antagonists attenuated the ethanol-evoked increases in myocardial catalase and ALDH2 activities, ERα blockade also inhibited myocardial catalase activity in the absence of ethanol. Ethanol-evoked elevation in myocardial ROS and enhancement of myocardial Akt, ERK1/2, eNOS and nNOS phosphorylation were attenuated by the 3 ER subtype antagonists. In conclusion, the findings support a greater role for ERα signaling in the E2-dependent myocardial oxidative stress and dysfunction caused by ethanol in proestrus rats.
Author Disclosures: F. Yao: None. A. A. Abdel-Rahman: None.
- © 2015 by American Heart Association, Inc.