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Am J Physiol Cell Physiol 278: C834-C844, 2000;
0363-6143/00 $5.00
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Vol. 278, Issue 4, C834-C844, April 2000

Gender-specific reduction in contractility and [Ca2+]i in vascular smooth muscle cells of female rat

Jason G. Murphy and Raouf A. Khalil

Department of Physiology and Biophysics and Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505

The hypothesis that vascular protection in females and its absence in males reflects gender differences in [Ca2+]i and Ca2+ 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 Ca2+), the resting length and [Ca2+]i were significantly different in intact males (64.5 ± 1.2 µm and 83 ± 3 nM) than in intact females (76.5 ± 1.5 µm and 64 ± 7 nM). In intact male WKY, phenylephrine (Phe, 10-5 M) caused transient increase in [Ca2+]i to 428 ± 13 nM followed by maintained increase to 201 ± 8 nM and 32% cell contraction. In intact female WKY, the Phe-induced [Ca2+]i transient was not significantly different, but the maintained [Ca2+]i (159 ± 7 nM) and cell contraction (26%) were significantly less than in intact male WKY. In Ca2+-free (2 mM EGTA) Hanks', Phe and caffeine (10 mM) caused transient increases in [Ca2+]i and contraction that were not significantly different between males and females. Membrane depolarization by 51 mM KCl caused 31% cell contraction and increased [Ca2+]i to 259 ± 9 nM in intact male WKY, which were significantly greater than a 24% contraction and 214 ± 8 nM [Ca2+]i in intact female WKY. Maintained Phe- and KCl-stimulated cell contraction and [Ca2+]i were significantly greater in SHR than WKY in all groups of rats. Reduction in cell contraction and [Ca2+]i in intact females compared with intact males was significantly greater in SHR (~30%) than WKY (~20%). No significant differences in cell contraction or [Ca2+]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 [Ca2+]i in SHR than WKY. Thus the basal, maintained Phe- and depolarization-induced [Ca2+]i and contraction of vascular smooth muscle triggered by Ca2+ entry from the extracellular space exhibit differences depending on gender and the presence or absence of female gonads. Cell contraction and [Ca2+]i due to Ca2+ release from the intracellular stores are not affected by gender or gonadectomy. Gender-specific reduction in contractility and [Ca2+]i in vascular smooth muscle of female rats is greater in SHR than WKY rats.

sex hormones; vascular smooth muscle; contraction; hypertension


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