Gender-specific reduction in contractility and [Ca(2+)](i) in vascular smooth muscle cells of female rat

Abstract

The hypothesis that vascular protection in females and its absence in males reflects gender differences in [Ca(2+)](i) and Ca(2+) mobilization mechanisms of vascular smooth muscle contraction was tested in fura 2-loaded aortic smooth muscle cells isolated from intact and gonadectomized male and female Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. In WKY cells incubated in Hanks' solution (1 mM Ca(2+)), the resting length and [Ca(2+)](i) were significantly different in intact males (64.5 +/- 1.2 microm and 83 +/- 3 nM) than in intact females (76.5 +/- 1.5 microm and 64 +/- 7 nM). In intact male WKY, phenylephrine (Phe, 10(-5) M) caused transient increase in [Ca(2+)](i) to 428 +/- 13 nM followed by maintained increase to 201 +/- 8 nM and 32% cell contraction. In intact female WKY, the Phe-induced [Ca(2+)](i) transient was not significantly different, but the maintained [Ca(2+)](i) (159 +/- 7 nM) and cell contraction (26%) were significantly less than in intact male WKY. In Ca(2+)-free (2 mM EGTA) Hanks', Phe and caffeine (10 mM) caused transient increases in [Ca(2+)](i) and contraction that were not significantly different between males and females. Membrane depolarization by 51 mM KCl caused 31% cell contraction and increased [Ca(2+)](i) to 259 +/- 9 nM in intact male WKY, which were significantly greater than a 24% contraction and 214 +/- 8 nM [Ca(2+)](i) in intact female WKY. Maintained Phe- and KCl-stimulated cell contraction and [Ca(2+)](i) were significantly greater in SHR than WKY in all groups of rats. Reduction in cell contraction and [Ca(2+)](i) in intact females compared with intact males was significantly greater in SHR ( approximately 30%) than WKY ( approximately 20%). No significant differences in cell contraction or [Ca(2+)](i) were observed between castrated males, ovariectomized (OVX) females, and intact males, or between OVX females with 17beta-estradiol implants and intact females. Exogenous application of 17beta-estradiol (10(-8) M) to cells from OVX females caused greater reduction in Phe- and KCl-induced contraction and [Ca(2+)](i) in SHR than WKY. Thus the basal, maintained Phe- and depolarization-induced [Ca(2+)](i) and contraction of vascular smooth muscle triggered by Ca(2+) entry from the extracellular space exhibit differences depending on gender and the presence or absence of female gonads. Cell contraction and [Ca(2+)](i) due to Ca(2+) release from the intracellular stores are not affected by gender or gonadectomy. Gender-specific reduction in contractility and [Ca(2+)](i) in vascular smooth muscle of female rats is greater in SHR than WKY rats.