Altered calcium dynamics do not account for attenuation of endothelium-derived hyperpolarizing factor-mediated dilations in the female middle cerebral artery.
OBJECTIVE
The contribution of endothelium-derived hyperpolarizing factor (EDHF) to ATP-mediated dilations is significantly attenuated in the rat middle cerebral artery of intact and estrogen-treated ovariectomized (OVX) females compared with males and vehicle-treated OVX females. Since an increase in endothelial calcium appears to be a critical prerequisite in the EDHF response, we tested the hypothesis that endothelial cell intracellular calcium ([Ca(2+)](i)) fails to reach sufficient levels to elicit robust EDHF-mediated dilations in females and that this effect is mediated by estrogen.


METHODS
Vascular diameter and [Ca(2+)](i) were measured concomitantly in perfused middle cerebral artery segments with the use of videomicroscopy and fura 2 fluorescence, respectively.


RESULTS
In the presence of N(G)-nitro-L-arginine methyl ester and indomethacin, the dilation to 10(-5) mol/L ATP was significantly reduced (P<0.05) in intact females (42+/-8%; n=6) and estrogen-treated OVX females (25+/-6%; n=9) compared with intact males (89+/-5%; n=6) and vehicle-treated OVX females (92+/-2%; n=7). Contrary to our initial hypothesis, endothelial cell [Ca(2+)](i) increased to comparable levels in intact females (461+/-116 nmol/L), estrogen-treated OVX females (417+/-50 nmol/L), intact males (421+/-77 nmol/L), and vehicle-treated OVX females (530+/-92 nmol/L). In response to luminal ATP (10(-5) mol/L), smooth muscle cell [Ca(2+)](i) decreased to a greater degree in males (37+/-4%; n=8) compared with females (21+/-5%; n=7) and in vehicle-treated OVX females (18+/-7%; n=7) compared with estrogen-treated OVX females (3+/-5%; n=9).


CONCLUSIONS
Our data suggest that loss of a factor coupling EDHF to reduction of ionized smooth muscle cell [Ca(2+)](i) accounts for the attenuated EDHF-mediated dilations in the female middle cerebral artery.
Golding
Elke M
EM
Department of Anesthesiology, Baylor College of Medicine, Houston, Texas, USA. egolding@bcm.tmc.edu
Ferens
Dorota M
DM
Marrelli
Sean P
SP
D000818:Animals; D001685:Biological Factors / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004343:Drug Implants / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D008297:Male; D018715:Microscopy, Video; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D020318:Rats, Long-Evans; D012737:Sex Factors; D014654:Vascular Patency / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001685:Biological Factors; D004343:Drug Implants; D005456:Fluorescent Dyes; C067410:endothelium-dependent hyperpolarization factor; D004958:Estradiol; D002118:Calcium