Gender Differences in Ca2+ Entry Mechanisms of Vasoconstriction in Wistar-Kyoto and Spontaneously Hypertensive Rats

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