Estrogen relaxation of coronary artery smooth muscle is mediated by
nitric oxide and cyclic gmp.
Darkow, David J., Luo Lu, and Richard E. White.
Department of Physiology and Biophysics, Wright State University
School of Medicine, Dayton, Ohio 45435
APStracts 4:0079H, 1997.
Estrogens are proposed to exert protection against cardiovascular
disease, and evidence now suggests this protection involves a direct
vasodilatory effect. We have shown previously that estrogen relaxes
endothelium-denuded porcine coronary arteries by opening the large
conductance, calcium- and voltage-activated potassium (BKCa) channel
of myocytes through cGMP-dependent phosphorylation (35). The present
study confirms these results, and now demonstrates that this
mechanism involves production of nitric oxide (NO). S-nitroso-N
-acetylpenicillamine (SNAP), a NO donor, or 8Br-cGMP mimicked the
effect of estrogen on BKCa channels. Furthermore, inhibition of
nitric oxide synthase (NOS), attenuated estrogen- or tamoxifen
-induced BKCa channel activity, and this effect was disinhibited by L
-arginine. Inhibition of guanylyl cyclase activity blocked the
stimulatory effect of estrogen, SNAP, or L-arginine on BKCa channels.
Furthermore, 17[beta]-estradiol stimulated accumulation of nitrite
and cyclic GMP in coronary myocytes. Therefore, we propose that
estrogen's vasodilatory effect on the coronary circulation is
mediated by NO. A portion of estrogen's beneficial cardiovascular
effects may be attributed to relaxation of vascular smooth muscle by
a process which involves NO- and cGMP-dependent stimulation of BKCa
channels.
Received 9 September 1996; accepted in final form 12 February
1997.
APS Manuscript Number H790-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 5 March 1997