Acute relaxant effects of 17-β-estradiol through non-genomic mechanisms in rabbit carotid artery

Estrogens could play a cardiovascular protective role not only by means of systemic effects but also by means of direct effects on vascular structure and function. We have studied the acute effects and mechanisms of action of 17-beta-estradiol on vascular tone of rabbit isolated carotid artery. 17-beta-Estradiol (10, 30, and 100 muM) elicited concentration-dependent relaxation of 50 mM KCl-induced active tone in male and female rabbit carotid artery. The stereoisonner 17-alpha-estradiol showed lesser relaxant effects in male rabbits. Endothelium removal did not modify relaxation induced by 17-beta-estradiol. The NO synthase inhibitor L-NAME (100 muM) only reduced significantly relaxation produced by 30 muM 17-beta-estradiol. Relaxation was not modified by the estrogen receptor antagonist ICI 182,780 (1 muM), the protein synthesis inhibitor cycloheximide (1 muM), and the selective K+ channel blockers charybdotoxin (0.1 muM) and glibenclamide (1 muM). CaCl2 (30 muM -10 mM) induced concentration-dependent contraction in rabbit carotid artery depolarized. by 50 mM KCl in Ca2+ free medium. Preincubation with 17-beta-estradiol (3, 10, 30, or 100 muM) or the L-type Ca2+ channel blocker nicardipine (0.01, 0.1, 1, or 10 nM) produced concentration-dependent inhibition of CaCl2-induced contraction. In conclusion, 17-beta-estradiol induces endothelium-independent relaxation of rabbit carotid artery, which is not mediated by classic estrogen receptor and protein synthesis activation. The relaxant effect is due to inhibition of extracellular Ca2+ influx to vascular smooth muscle, but activation of K+ efflux is not involved. Relatively high pharmacological concentrations of estrogen causing relaxation preclude acute vasoactive effects of plasma levels in the carotid circulation. (C) 2002 Elsevier Science Inc. All rights reserved.