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(Stroke. 2002;33:2972.)
© 2002 American Heart Association, Inc.

Original Contributions

Altered Calcium Dynamics Do Not Account for Attenuation of Endothelium-Derived Hyperpolarizing Factor–Mediated Dilations in the Female Middle Cerebral Artery

From the Department of Anesthesiology, Baylor College of Medicine, Houston, Tex.

Correspondence to Elke M. Golding, PhD, Department of Anesthesiology, Baylor College of Medicine, One Baylor Plaza, Suite 434D, Houston, TX 77030. E-mail egolding{at}bcm.tmc.edu

Background and Purpose— 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 ([Ca²⁺]_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 [Ca²⁺]_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 [Ca²⁺]_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 [Ca²⁺]_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 [Ca²⁺]_i accounts for the attenuated EDHF-mediated dilations in the female middle cerebral artery.

Key Words: brain • endothelium • endothelium-derived factors • gender • rats

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