title: Estrogen alters relative contributions of nitric oxide and cyclooxygenase products to endothelium-dependent vasodilation.
abstract: The purpose of this study was to determine the effects of in vivo estrogen manipulations on mechanisms of endothelium-dependent vasodilation. Ovary-intact, ovariectomized (OVX), or OVX with estrogen replacement (OVX + E(2)) female Sprague-Dawley rats were studied (n = 8). Mesenteric arteries (approximately 300 microm) were isolated, cannulated, and pressurized to 60 mm Hg in an arteriograph containing bicarbonate buffer and vessel diameter was monitored. Concentration-response curves to the endothelium-dependent histamine H(1) agonist 2-thiazolylethylamine (2-TEA; 1 nM-100 microM) and to acetylcholine (1 nM-10 microM) were performed in preconstricted arteries. The effect of Nomega-nitro-L-arginine (LNA; 100 microM) or LNA + indomethacin (INDO) (10 microM) on agonist-induced vasodilation was determined. There was no difference between treatment groups in the sensitivity of mesenteric arteries to 2-TEA or acetylcholine. LNA produced a significant decrease in sensitivity to 2-TEA in arteries from ovary-intact and OVX + E(2) rats but not in those from OVX rats. The addition of INDO produced a small additional decrease in sensitivity to 2-TEA in arteries from ovary-intact rats, a significant decrease in OVX, and no shift in OVX + E(2). LNA + INDO produced a similar degree of inhibition of the 2-TEA response in the three treatment groups. In contrast, when acetylcholine was used, the decrease in sensitivity produced by LNA or LNA + INDO was similar in the three rat groups. We conclude that estrogen increases the nitric oxide component of endothelium-dependent dilation and decreases the cyclooxygenase component. These effects of estrogen appear to be agonist-specific. Our findings suggest that estrogen modulates cross talk between the nitric oxide synthase and cyclooxygenase pathways of vasodilation.
authors.affiliation: Department of Pharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA.
authors.forename: J
authors.initials: J
authors.lastname: Case
authors.forename: C A
authors.initials: CA
authors.lastname: Davison
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D010052:Ovariectomy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D004967:Estrogens; D013844:Thiazoles; C029345:2-(2-aminoethyl)thiazole; D019335:Nitroarginine; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine; D007213:Indomethacin