Estrogen replacement enhances EDHF-mediated vasodilation of mesenteric and uterine resistance arteries: role of endothelial cell Ca2+

Burger NZ, Kuzina OY, Osol G, Gokina NI. Estrogen replacement enhances EDHF-mediated vasodilation of mesenteric and uterine resistance arteries: role of endothelial cell Ca2+. Am J Physiol Endocrinol Metab 296: E503-E512, 2009. First published January 6, 2009; doi:10.1152/ajpendo.90517.2008.-Endothelium-derived hyperpolarizing factor (EDHF) plays an important role in the regulation of vascular microcirculatory tone. This study explores the role of estrogen in controlling EDHF-mediated vasodilation of uterine resistance arteries of the rat and also analyzes the contribution of endothelial cell (EC) Ca2+ signaling to this process. A parallel study was also performed with mesenteric arteries to provide comparison with a nonreproductive vasculature. Mature female rats underwent ovariectomy, with one half receiving 17 beta-estradiol replacement (OVX + E) and the other half serving as estrogen-deficient controls (OVX). Uterine or mesenteric resistance arteries were harvested, cannulated, and pressurized. Nitric oxide and prostacyclin production were inhibited with 200 mu M N-G-nitro-L-arginine and 10 mu M indomethacin, respectively. ACh effectively dilated the arteries preconstricted with phenylephrine but failed to induce dilation of vessels preconstricted with high-K+ solution. ACh EC50 values were decreased by estrogen replacement by five- and twofold in uterine and mesenteric arteries, respectively. As evidenced by fura-2-based measurements of EC cytoplasmic Ca2+ concentration ([Ca2+](i)), estrogen replacement was associated with increased basal and ACh-stimulated EC [Ca2+](i) rise in uterine, but not mesenteric, vessels. These data demonstrate that EDHF contributes to endothelium-dependent vasodilation of uterine and mesenteric resistance arteries and that estrogen controls EDHF-elated mechanism(s) more efficiently in reproductive vs. nonreproductive vessels. Enhanced endothelial Ca2+ signaling may be an important underlying mechanism in estrogenic modulation of EDHF-mediated vasodilation in small resistance uterine arteries.