Isoproterenol amplifies 17β-estradiol-mediated vasorelaxation: role of endothelium/nitric oxide and cyclic AMP

Abstract

Estrogen exerts cardiac protection via multiple cellular mechanisms. Estrogen modifies vasodilatation induced by certain relaxants such as beta-adrenoceptor agonists. However, little is known whether low concentrations of beta-adrenoceptor agonists would reciprocally influence the acute relaxant response to estrogen. The present study was designed to investigate the synergistic interaction between isoproterenol and 17 beta-estradiol, and 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 using a force-displacement Grass transducer. In 9,11-dideoxy-11 alpha, 9 alpha-epoxy-methanoprostaglandin F(2 alpha)-preconstricted endothelium-intact rings, 17 beta-estradiol induced relaxations with pD(2) of 5.06 +/- 0.06. Pretreatment of endothelium-intact rings with isoproterenol (1-3 x 10(-9) M, 1 h incubation time) significantly enhanced 17 beta-estradiol-induced relaxation. This effect was inhibited by Rp-cGMPS triethylamine (3 x 10(-6) M), and abolished in the presence of 3 x 10(-5) M N(G)-nitro-L-arginine methyl ester or in endothelium-denuded rings. The effect of isoproterenol was antagonized by propranolol (3 x 10(-6) M), ICI 118,551 (3 x 10(-6) M), but not by atenolol (10(-5) M). Rp-cAMPS triethylamine (3 x 10(-6) M) abolished the effect of isoproterenol. Besides, exposure to 3 x 10(-9) M forskolin for 1 h also potentiated the relaxant response to 17 beta-estradiol. In endothelium-intact rat mesenteric arteries pretreatment with low concentrations of isoproterenol enhanced the acute relaxant response to 17 beta-estradiol. This enhancement was dependent on the presence of endothelium and abolished by L-NAME via a beta(2)-adrenoceptor-mediated cyclic AMP-dependent mechanism.