Estrogen replacement modulates resistance artery smooth muscle and endothelial alpha2-adrenoceptor reactivity

The purpose of this study was to evaluate the effects of estrogen replacement on ovariectomized rats on the reactivity to alpha2-adrenoceptor activation, and to analyze the role of the endothelium in modulating this response. Third order branches of the superior mesenteric artery from ovariectomized untreated (OvX) and estrogen-replaced (E2) Sprague-Dawley rats were cannulated and pressurized to 50 mmHg. Under relaxed conditions (0.1 mM papaverine), there were no differences in lumen diameter. Intact vessels from E2 rats were unresponsive to clonidine (0.01-10 microM); incubation in indomethacin (1 microM), a cyclooxygenase inhibitor, produced intermediate constriction that was significantly augmented by L-NNA (0.3 mM), a NO synthase inhibitor, or by endothelial denudation. Conversely, intact vessels from OvX animals constricted to clonidine in a concentration-dependent manner. This effect was significantly diminished by endothelial removal or indomethacin, but was not affected by L-NNA. Yohimbine (1 microM), an beta2 receptor antagonist, significantly diminished arterial sensitivity to, and efficacy of clonidine. These results suggest that estrogen replacement enhanced vasoconstriction induced by smooth muscle alpha2 adrenoceptor activation, although this effect was obscured in intact vessels due to an overriding influence of endothelial dilator substances, primarily NO. In arteries from OvX animals, smooth muscle was less sensitive to alpha2 agonist stimulation, however, the release of a vasoconstrictor prostanoid from the endothelium was predominant, and induced significant vasoconstriction.