Abstract

Estrogen exerts vasorelaxation and cardiac protection via multiple cellular mechanisms. Estrogen modifies vasodilatation induced by certain relaxants such as s-adrenoceptor agonists. However, little is known whether low concentrations of s-adrenoceptor agonists would also influence the acute relaxant response to estrogen. The present study was designed to investigate the synergistic interaction between isoproterenol and 17s-estradiol, and to study the role of endothelium and cyclic AMP-dependent pathway in this interaction. Changes in vessel tone of the isolated rat mesenteric artery rings were measured by force-displacement Grass transducer. In 9,11-dideoxy-11α, 9α-epoxy-methanoprostaglandin F2α- preconstricted endothelium-intact rings, 17s-estradiol induced concentration-dependent relaxation with pD2 of 5.074 ± 0.043. Pretreatment of endothelium-intact rings with isoproterenol (1-3 × 10-9 M, 1-h incubation time) significantly enhanced 17β-estradiol-induced relaxation. Longer incubation (2.5 h) did not produce further amplifying effect. This effect was inhibited by Rp-cGMPS triethylamine (3 × 10-6 M), and disappeared in the presence of 3 × 10-5 M NG-nitro-L-arginine methyl ester or in the endothelium-denuded rings. The effect of isoproterenol was partially antagonized by propranolol (3 × 10-6 M), ICI 118,551 (3 × 10-6 M) but not by atenolol (10-5 M). None of three β-adrenoceptor antagonists affected 17s-estradiol-induced relaxation in the absence of isoproterenol. Rp-cAMPS triethylamine (3 × 10-6 M) abolished the effect of isoproterenol. Besides, exposure to 3 × 10-9 M forskolin for 1 h also potentiated the relaxant response to 17β-estradiol. In summary, this isoproterenol enhancement was dependent on the presence of endothelium and abolished by L-NAME via a β2-adrenoceptor-mediated cyclic AMP-dependent mechanism. These data also indicate the possible existence of cyclic AMP-dependent nitric oxide-producing pathway in the regulation of the vascular response to vasodilators. (supported by UPGC Direct Grant)

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