Jg. Murphy et Ra. Khalil, Gender-specific reduction in contractility and [Ca2+](i) in vascular smooth muscle cells of female rat, AM J P-CELL, 278(4), 2000, pp. C834-C844
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 sm
ooth muscle cells isolated from intact and gonadectomized male and female W
istar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. In WKY cells i
ncubated in Hanks' solution (1 mM Ca2+), the resting length and [Ca2+](i) w
ere significantly different in intact males (64.5 +/- mu m and 83 +/- 3 nM)
than in intact females (76.5 +/- 1.5 mu m 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% ce
ll contraction. In intact female WKY, the Phe-induced [Ca2+](i) transient w
as 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 transien
t increases in [Ca2+](i) and contraction that were not significantly differ
ent 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 al
l groups of rats. Reduction in cell contraction and [Ca2+](i) in intact fem
ales compared with intact males was significantly greater in SHR (similar t
o 30%) than WKY (similar to 20%). No significant differences in cell contra
ction or [Ca2+](i) were observed between castrated males, ovariectomized (O
VX) females, and intact males, or between OVX females with 17 beta-estradio
l implants and Intact females. Exogenous application of 17 beta-estradiol (
10(-8) M) to cells from OVX females caused greater reduction in Phe- and KC
l-induced contraction and [Ca2+](i) in SHR than WKY. Thus the basal, mainta
ined Phe- and depolarization-indueed [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 gonad
s. Cell contraction and [Ca2+](i) due to Ca2+ release from the intracellula
r stores are not affected by gender or gonadectomy. Gender-specific reducti
on in contractility and [Ca2+](i) in vascular smooth muscle of female rats
is greater in SHR than WKY rats.