Relaxant effects of 17-beta-estradiol in cerebral arteries through Ca2+ entry inhibition

Estrogens account for gender differences in the incidence and outcome of st roke, but it remains unclear to what extent neuroprotective effects of estr ogens are because of parenchymal or vascular actions. Because reproductive steroids have vasoactive properties, the authors assessed the effects and m echanisms of action of 17-beta -estradiol in rabbit isolated bas ilar arter y. Cumulative doses of 17-beta -estradiol (0.3 mu mol/L to 0.1 mmol/L) indu ced concentration-dependent relaxation that was larger in basilar than caro tid artery, in male than female basilar artery, and in KCl-precontracted th an UTP-precontracted male basilar artery. Endothelium removal did not modif y relaxation induced by 17-beta -estradiol in basilar artery, whereas relax ation induced by acetylcholine (1 nmol/L to 0.1 mmol/L) was almost abolishe d. Neither the estrogen receptor antagonist ICI 182,780 (1 mu mol/L), nor t he protein synthesis inhibitor cycloheximide (l mu mol/L) affected 17-beta -estradiol-induced relaxations. Relaxations induced by the K+ channel opene rs NS1619 and pinacidil in the same concentration range were greater and lo wer, respectively, when compared with relaxation to 17-beta -estradiol, whi ch was not significantly modified by incubation with the K+ channel blocker s charybdotoxin (1 nmol/L and 0.1 mu mol/L) or glibenclamide (10 nmol/L and 1 mu mol/L). Preincubation with 17-beta -estradiol (3 to 100 mu mol/L) pro duced concentration-dependent inhibition of CaCl2-induced contraction, with less potency than the Ca2+ entry blocker nicardipine (0.01 to 10 nmol/L). The authors conclude that 17-beta -estradiol induces endothelium-independen t relaxation of cerebral arteries with tissue and Sender selectivity. The r elaxant effect is because of inhibition of extracellular Ca2+ influx to vas cular smooth muscle, but activation of estrogen receptors, protein synthesi s, or K+ efflux are not involved. Relatively high pharmacologic concentrati ons of 17-beta -estradiol causing relaxation preclude acute vascular effect s of physiologic circulating levels on the cerebral circulation.