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- Title
Isoproterenol amplifies 17β-estradiol-mediated vasorelaxation: role of endothelium/nitric oxide and cyclic AMP
- Authors
Chan, Hoi Yun; Yao, Xiaoqiang; Tsang, Suk Ying; Bourreau, Jean-Pierre; Chan, Franky Leung; Huang, Yu
- Abstract
<B>Objectives:</B> Estrogen exerts cardiac protection via multiple cellular mechanisms. Estrogen modifies vasodilatation induced by certain relaxants such as β-adrenoceptor agonists. However, little is known whether low concentrations of β-adrenoceptor agonists would reciprocally influence the acute relaxant response to estrogen. The present study was designed to investigate the synergistic interaction between isoproterenol and 17β-estradiol, and the role of endothelium and cyclic AMP-dependent pathway in this interaction. <B>Methods:</B> Changes in vessel tone of the isolated rat mesenteric artery rings were measured using a force–displacement Grass transducer. <B>Results:</B> In 9,11-dideoxy-11α, 9α-epoxy-methanoprostaglandin F2α-preconstricted endothelium-intact rings, 17β-estradiol induced relaxations with pD2 of 5.06±0.06. Pretreatment of endothelium-intact rings with isoproterenol (1–3×10−9 M, 1 h incubation time) significantly enhanced 17β-estradiol-induced relaxation. This effect was inhibited by Rp-cGMPS triethylamine (3×10−6 M), and abolished in the presence of 3×10−5 M NG-nitro-l-arginine methyl ester or in endothelium-denuded rings. The effect of isoproterenol was antagonized by propranolol (3×10−6 M), ICI 118,551 (3×10−6 M), but not by atenolol (10−5 M). 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. <B>Conclusion:</B> In endothelium-intact rat mesenteric arteries pretreatment with low concentrations of isoproterenol enhanced the acute relaxant response to 17β-estradiol. This enhancement was dependent on the presence of endothelium and abolished by l-NAME via a β2-adrenoceptor-mediated cyclic AMP-dependent mechanism.
- Subjects
ADRENERGIC beta agonists; ISOPROTERENOL; ESTRADIOL
- Publication
Cardiovascular Research, 2002, Vol 53, Issue 3, p627
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1016/S0008-6363(01)00498-9