Effect of estrogen replacement on vasoconstrictor responses in rat mesenteric arteries

Abstract

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. 17β-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 μmol/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 (EC50=0.90±0.17 vs 0.44±0.08 μmol/L, P<0.05). After incubation with N(G)-monomethyl-L arginine, the EC50 of phenylephrine significantly decreased in both groups, but a significant difference remained between the 2 groups (EC50=0.41±0.08 vs 0.28±0.02 μmol/L, P<0.05). Importantly, Western immunoblotting demonstrated that the expression of α1-adrenergic receptors was significantly suppressed by estradiol replacement. We conclude that estrogen may have a specific effect on adrenergic vasoconstriction by modulating its receptors.