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

Autor: Raouf A. Khalil, Jason G. Murphy
Rok vydání: 2001
Předmět:
Zdroj: American journal of physiology. Cell physiology. 278(4)
ISSN: 0363-6143
Popis: The hypothesis that vascular protection in females and its absence in males reflects gender differences in [Ca2+]iand 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+]iwere 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, 10−5M) caused transient increase in [Ca2+]ito 428 ± 13 nM followed by maintained increase to 201 ± 8 nM and 32% cell contraction. In intact female WKY, the Phe-induced [Ca2+]itransient 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+]iand contraction that were not significantly different between males and females. Membrane depolarization by 51 mM KCl caused 31% cell contraction and increased [Ca2+]ito 259 ± 9 nM in intact male WKY, which were significantly greater than a 24% contraction and 214 ± 8 nM [Ca2+]iin intact female WKY. Maintained Phe- and KCl-stimulated cell contraction and [Ca2+]iwere significantly greater in SHR than WKY in all groups of rats. Reduction in cell contraction and [Ca2+]iin intact females compared with intact males was significantly greater in SHR (∼30%) than WKY (∼20%). No significant differences in cell contraction or [Ca2+]iwere observed between castrated males, ovariectomized (OVX) females, and intact males, or between OVX females with 17β-estradiol implants and intact females. Exogenous application of 17β-estradiol (10−8M) to cells from OVX females caused greater reduction in Phe- and KCl-induced contraction and [Ca2+]iin SHR than WKY. Thus the basal, maintained Phe- and depolarization-induced [Ca2+]iand 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+]idue to Ca2+release from the intracellular stores are not affected by gender or gonadectomy. Gender-specific reduction in contractility and [Ca2+]iin vascular smooth muscle of female rats is greater in SHR than WKY rats.
Databáze: OpenAIRE