Gender differences in Ca2+ entry mechanisms of vasoconstriction in Wistar-Kyoto and spontaneously hypertensive rats

We investigated whether putative vascular protection against hypertension in females reflects differences in the Ca2+ mobilization mechanisms of vasoconstriction depending on the gender and the status of the gonads. Active stress and Ca-45(2+) 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 Ca2+), both phenylephrine (10(-5) mol/L) and membrane depolarization by 96 mmol/L KCl caused significant increases in active stress and Ca-45(2+) influx, In intact female WKY, the phenylephrine- and KCl-induced stress and Ca-45(2+) influx were significantly reduced. In Ca2+-free (2 mmol/L EGTA) Krebs' solution, stimulation of aortic strips with phenylephrine or caffeine (25 mmol/L) to induce Ca2+ 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 Ca-45(2+) influx were significantly greater than those in WKY in all groups of rats. The reduction in stress and Ca2+ entry in intact females compared with intact males was greater in SHR than in WKY. The contractile responses and Ca2+ 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 Ca2+ entry in ovariectomized female WKY or SHR with 17 beta-estradiol implant were not significantly different from the respective responses in intact females. Thus, the phenylephrine- and depolarization-induced vascular reactivity and Ca2+ entry in vascular smooth muscle are dependent on gender and on the presence or absence of functional female gonads, Ca2+ release from intracellular stores is not affected by gender or gonadectomy. The gender-specific changes in vascular reactivity and Ca2+ entry are augmented in hypertension.