Mechanisms of estrogen-induced vasodilation: in vivo studies in canine coronary conductance and resistance arteries

Cardiovascular Research Institute, University of California at San Francisco, USA.

OBJECTIVES. We sought to examine the immediate vasodilator effect of intracoronary estrogen on epicardial and resistance coronary arteries in 19 dogs. BACKGROUND. Although estrogen reportedly dilates coronary arteries in vitro, the site and mechanisms of its action have not been fully defined in vivo. METHODS. Epicardial coronary artery dimensions and coronary flow velocity were assessed using simultaneous intracoronary two-dimensional and Doppler ultrasound. RESULTS. Estrogen (0.1 and 1 mumol/liter) induced a significant increase in coronary cross-sectional area, flow velocity and volumetric blood flow. Estrogen-induced vasodilation was not influenced either by pretreatment with N omega-nitro-L-arginine methyl ester (L-NAME) (100 mumol/liter intracoronary), indomethacin (5 mg/kg body weight intravenously), propranolol (0.75 mg/kg intravenously) or the classic estrogen receptor antagonist ICI 182,780 (10 mumol/liter). Balloon denudation of the endothelium did not attenuate estrogen-induced epicardial vasodilation. Pretreatment with glibenclamide (10 mumol/liter) attenuated estrogen-induced vasodilation only in epicardial arteries, as did verapamil (0.1 mumol/liter). Estrogen had no effect on a phenylephrine dose-response curve in either epicardial coronary arteries or the microcirculation. CONCLUSIONS. Acute estrogen-induced dilation in canine coronary arteries is endothelium independent and is not mediated by the classic intracellular estrogen receptor but through non-genomic mechanisms, presumably at the membrane level, which in epicardial arteries may include effects on adenosine triphosphate-sensitive potassium or calcium channels, or both.

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