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

Burger NZ, Kuzina OY, Osol G, Gokina NI. Estrogen replacement enhances EDHF-mediated vasodilation of mesenteric and uterine resistance arteries: role of endothelial cell Ca . 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) Ca 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 -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 M N-nitro-L-arginine and 10 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 fiveand twofold in uterine and mesenteric arteries, respectively. As evidenced by fura-2-based measurements of EC cytoplasmic Ca concentration ([Ca ]i), estrogen replacement was associated with increased basal and ACh-stimulated EC [Ca ]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 EDHFrelated mechanism(s) more efficiently in reproductive vs. nonreproductive vessels. Enhanced endothelial Ca signaling may be an important underlying mechanism in estrogenic modulation of EDHFmediated vasodilation in small resistance uterine arteries.