title: Isoproterenol amplifies 17 beta-estradiol-mediated vasorelaxation: role of endothelium/nitric oxide and cyclic AMP.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Changes in vessel tone of the isolated rat mesenteric artery rings were measured using a force-displacement Grass transducer.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology, Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Hoi Yun
authors.initials: HY
authors.lastname: Chan
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yao
authors.forename: Suk Ying
authors.initials: SY
authors.lastname: Tsang
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bourreau
authors.forename: Franky Leung
authors.initials: FL
authors.lastname: Chan
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D011412:Propanolamines; D009569:Nitric Oxide; C026777:ICI 118551; D004958:Estradiol; D001262:Atenolol; D011433:Propranolol; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester