GENDER DIFFERENCES IN CORONARY-ARTERY DIAMETER INVOLVE ESTROGEN, NITRIC-OXIDE, AND CA2-DEPENDENT K+ CHANNELS()

During their reproductive years, women have a much lower incidence of coronary heart disease compared with men of similar age. Estrogen appe ars to be largely responsible for this decrease in cardiovascular mort ality in women. In the present study, isolated pressurized coronary ar teries from rats were used to assess the role of gender and circulatin g estrogen on coronary vascular function. Pressure-induced constrictio ns (''myogenic tone'') were greater (approximate to 2-fold) in isolate d coronary arteries from estrogen-deficient male or ovariectomized (OV X) rats compared with similar arteries obtained from female rats or OV X rats receiving physiological levels of estrogen replacement (OVX+E g roup). These differences in coronary artery diameter were abolished by removal of the vascular endothelium or chemical inhibition of NO synt hase. The anti-estrogen, tamoxifen, increased pressure-induced constri ctions of coronary arteries from female and OVX+E rats. Dilations of p ressurized coronary arteries from female and OVX animals to sodium nit roprusside, a nitrovasodilator that generates NO, were reduced by >50% by iberiotoxin (IBTX), an inhibitor of Ca2+-dependent K+ (K-Ca) chann els. Sodium nitroprusside (10 mu mol/L) hyperpolarized col onary arter ies by 13 +/- 2 mV, an effect that was greatly diminished (approximate to 80%), by IBTX. Coronary arteries isolated from female rats produce d greater constrictions in response to IBTX and KT 5823, an inhibitor of cGMP-dependent protein kinase, compared with coronary arteries from OVX rats, cGMP-dependent protein kinase increased the activity of K-C a channels 16.5 +/- 5-fold in excised membrane patches from smooth mus cle cells enzymatically isolated From these small coronary arteries. W e propose that physiological levels of circulating 17 beta-estradiol e levate basal NO release front the endothelial cells, which increases t he diameter of pressurized coronary arteries. Further, our results sug gest that part of the effect of this NO is through activation of K-Ca channels in the smooth muscle cells of thc coronary arteries.