title: Estrogen replacement enhances EDHF-mediated vasodilation of mesenteric and uterine resistance arteries: role of endothelial cell Ca2+.
abstract: 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(2+) 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 17beta-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 microM N(G)-nitro-l-arginine and 10 microM indomethacin, respectively. ACh effectively dilated the arteries preconstricted with phenylephrine but failed to induce dilation of vessels preconstricted with high-K(+) solution. ACh EC(50) 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 Ca(2+) concentration ([Ca(2+)](i)), estrogen replacement was associated with increased basal and ACh-stimulated EC [Ca(2+)](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-related mechanism(s) more efficiently in reproductive vs. nonreproductive vessels. Enhanced endothelial Ca(2+) signaling may be an important underlying mechanism in estrogenic modulation of EDHF-mediated vasodilation in small resistance uterine arteries.
authors.affiliation: Department of Obstetrics, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Natalie Z
authors.initials: NZ
authors.lastname: Burger
authors.forename: Olga Y
authors.initials: OY
authors.lastname: Kuzina
authors.forename: George
authors.initials: G
authors.lastname: Osol
authors.forename: Natalia I
authors.initials: NI
authors.lastname: Gokina
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D010052:Ovariectomy; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000098:blood supply*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D004958:Estradiol; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium