We investigated whether putative vascular protection against hypertension in females reflects differences in the Ca 2ϩ mobilization mechanisms of vasoconstriction depending on the gender and the status of the gonads. Active stress and 45 Ca 2ϩ influx were measured in aortic strips isolated from intact and gonadectomized male and female Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In aortic strips of intact male WKY incubated in normal Krebs' solution (2.5 mmol/L Ca 2ϩ ),

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... th phenylephrine (10 Ϫ5 mol/L) and membrane depolarization by 96 mmol/L KCl caused significant increases in active stress and 45 Ca 2ϩ influx. In intact female WKY, the phenylephrine-and KCl-induced stress and 45 Ca 2ϩ influx were significantly reduced. In Ca 2ϩ -free (2 mmol/L EGTA) Krebs' solution, stimulation of aortic strips with phenylephrine or caffeine (25 mmol/L) to induce Ca 2ϩ release from intracellular stores caused a transient increase in stress that was not significantly different between males and females. In SHR, the phenylephrine-and KCl-induced stress and 45 Ca 2ϩ influx were significantly greater than those in WKY in all groups of rats. The reduction in stress and Ca 2ϩ entry in intact females compared with intact males was greater in SHR than in WKY. The contractile responses and Ca 2ϩ entry in castrated male and ovariectomized female WKY or SHR were not significantly different from the respective responses in intact males. The contractile responses and Ca 2ϩ entry in ovariectomized female WKY or SHR with 17␤-estradiol implant were not significantly different from the respective responses in intact females. Thus, the phenylephrine-and depolarization-induced vascular reactivity and Ca 2ϩ entry in vascular smooth muscle are dependent on gender and on the presence or absence of functional female gonads. Ca 2ϩ release from intracellular stores is not affected by gender or gonadectomy. The gender-specific changes in vascular reactivity and Ca 2ϩ entry are augmented in hypertension. (Hypertension. 1999;34[part 2]:931-936.)