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

We investigated whether putative vascular protection against hypertension i n females reflects differences in the Ca2+ mobilization mechanisms of vasoc onstriction depending on the gender and the status of the gonads. Active st ress and Ca-45(2+) influx were measured in aortic strips isolated from inta ct and gonadectomized male and female Wistar-Kyoto rats (WKY) and spontaneo usly hypertensive rats (SHR). In aortic strips of intact male WKY incubated in normal Krebs' solution (2.5 mmol/L Ca2+), both phenylephrine (10(-5) mo l/L) and membrane depolarization by 96 mmol/L KCl caused significant increa ses in active stress and Ca-45(2+) influx, In intact female WKY, the phenyl ephrine- and KCl-induced stress and Ca-45(2+) influx were significantly red uced. In Ca2+-free (2 mmol/L EGTA) Krebs' solution, stimulation of aortic s trips with phenylephrine or caffeine (25 mmol/L) to induce Ca2+ release fro m intracellular stores caused a transient increase in stress that was not s ignificantly different between males and females. In SHR, the phenylephrine - and KCl-induced stress and Ca-45(2+) influx were significantly greater th an those in WKY in all groups of rats. The reduction in stress and Ca2+ ent ry in intact females compared with intact males was greater in SHR than in WKY. The contractile responses and Ca2+ entry in castrated male and ovariec tomized female WKY or SHR were not significantly different from the respect ive responses in intact males. The contractile responses and Ca2+ entry in ovariectomized female WKY or SHR with 17 beta-estradiol implant were not si gnificantly 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 presen ce or absence of functional female gonads, Ca2+ release from intracellular stores is not affected by gender or gonadectomy. The gender-specific change s in vascular reactivity and Ca2+ entry are augmented in hypertension.