Gender differences in Ca(2+) entry mechanisms of vasoconstriction in Wistar-Kyoto and spontaneously hypertensive rats.

摘要

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 17beta-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.