In vivo loss of estrogen increases Ca2+ influx via voltage-gated calcium channels in mesenteric arterial smooth muscle cells.

摘要

The presence of estrogen in premenopausal women protects against the development of vascular dysfunctions, such as hypertension. Estrogen is a potent vasodilator and decreases vascular tone by inhibiting voltage-gated, L-type Ca2+ (CaL) channels. Previous studies from our lab demonstrated a slight increase in CaL channel expression in mesenteric arteries (resistance arteries) from ovariectomized (OVX) mice. Therefore, the purpose of this study was to determine if the in vivo loss of estrogen will increase Ca2+ influx into arterial smooth muscle cells. This study utilized mesenteric arterial smooth muscle cells isolated from twelve-week old mice that had been ovariectomized at eight weeks of age. Our data suggest that the endogenous estrogen depletion increases Ca2+ influx via CaL channels. This study also evaluated the impact of the sarcoplasmic reticulum (SR) on the OVX-enhanced Ca L channel-induced Ca2+ influx, and found that the Ca L channel-induced Ca2+ influx was enhanced when the SR is functional. The morphometric parameters of this mouse model were also assessed. We found that although estrogen depletion does not increase heart weight, weight gain was significantly increased in OVX mice. These results suggest that the loss of in vivo estrogen leads to the enhanced influx of Ca2+ into arterial cells which may lead to a chronic elevation of vascular tone in postmenopausal women.