Effect of estrogen replacement on vasoconstrictor responses in rat mesenteric arteries.
Recent studies have shown that estrogen can increase endothelial nitric oxide synthase expression and/or activity and that nitric oxide may play a role in attenuating vasoconstrictor responses. Yet there are still controversies in this field. Our hypothesis was that the role of nitric oxide in modulating vasoconstrictor responses in estrogen-replaced animals depends on the agonist. The aim of the study was to determine the effect of long-term estrogen replacement on vascular reactivity of resistance-sized mesenteric arteries in ovariectomized rats with the use of a variety of vasoconstrictors. Female Sprague-Dawley rats were ovariectomized at 11 weeks of age. 17beta-estradiol pellets (0.5 mg/pellet) were implanted in the estrogen-replaced group (n=9) for 4 weeks; placebo pellets were used in the ovariectomized group (n=10). Resistance-sized mesenteric arteries were dissected and mounted onto a dual-chamber arteriograph system. Estradiol replacement did not alter the response of mesenteric arteries to either arginine vasopressin or the thromboxane mimetic U46619. Inhibition of nitric oxide synthase with N(G)-monomethyl-L-arginine (100 micromol/L) did not modulate these vasoconstrictor responses in either group of rats. In contrast, the dose-response curve of the adrenergic agonist phenylephrine was significantly attenuated for the estradiol-replaced rats compared with the ovariectomized group (EC(50)=0.90+/-0.17 vs 0.44+/-0.08 micromol/L, P<0.05). After incubation with N(G)-monomethyl-L-arginine, the EC(50) of phenylephrine significantly decreased in both groups, but a significant difference remained between the 2 groups (EC(50)=0.41+/-0.08 vs 0.28+/-0.02 micromol/L, P<0.05). Importantly, Western immunoblotting demonstrated that the expression of alpha(1)-adrenergic receptors was significantly suppressed by estradiol replacement. We conclude that estrogen may have a specific effect on adrenergic vasoconstriction by modulating its receptors.
Zhang
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Perinatal Research Centre, Departments of Ob/Gyn and Physiology, University of Alberta, Edmonton, Alberta, Canada.
Davidge
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D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000032:analysis; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D010656:Phenylephrine; D009569:Nitric Oxide; D004958:Estradiol; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid