ETHINYL ESTRADIOL ACUTELY ATTENUATES ABNORMAL CORONARY VASOMOTOR RESPONSES TO ACETYLCHOLINE IN POSTMENOPAUSAL WOMEN

Background Estrogen administration in postmenopausal women is associat ed with a 50% reduction in the clinical manifestations of coronary art ery disease. The mechanisms are not known, although one potential expl anation is estrogen-induced modulation of coronary vasoreactivity. Ace tylcholine is an endothelium-dependent vasodilator that may be used to assess coronary vasoreactivity and elicits coronary responses that pa rallel those found with common daily vasomotor stimuli. Therefore, we tested whether estrogen attenuates abnormal coronary vasomotor respons es to acetylcholine in postmenopausal women. Methods and Results Acety lcholine-induced changes in coronary flow, resistance, and cross-secti onal area were determined before and 15 minutes after intravenous admi nistration of ethinyl estradiol (EE, 35 mu g) in 15 postmenopausal wom en. The influence of estrogen an basal coronary flow, resistance, and epicardial cross-sectional area was also assessed by measuring these p arameters before and after EE or placebo administration in 33 women. E strogen altered basal coronary vasomotor tone in 22 women as manifeste d by an EE-induced 23.3+/-4.5% (mean+/-SEM) increase (P<.01) in corona ry flow, a 15.0+/-3.2% decrease (P<.01) in resistance, and a 20.0+/-6. 5% increase (P=.02) in epicardial cross-sectional area. Placebo admini stration in 11 women did not change these parameters. Estrogen also at tenuated abnormal coronary vasomotor responses to acetylcholine. Seven women who exhibited a paradoxical acetylcholine-induced decrease in c oronary how (-33.5+/-12.3%, P<.01) and increase in resistance (38.9+/- 14.1%, P=.05) and seven who had an abnormal acetylcholine-induced decr ease in epicardial cross-sectional area (-14.2+/-4.4%; P=.04) did not have acetylcholine-induced changes in these parameters after EE admini stration. Acetylcholine-induced flow, resistance, and cross-sectional area responses before and after EE were significantly different (P<.01 , P=.02, and P=.02, respectively). Normal coronary responses to acetyl choline were not affected by EE administration. Conclusions EE attenua tes abnormal coronary vasomotor responses to acetylcholine in postmeno pausal women. EE also decreases basal coronary vasomotor tone as manif ested by increased coronary flow, decreased resistance, and increased epicardial cross-sectional area. These acute effects of estrogen on co ronary vasoreactivity may explain, in part, the cardioprotective effec ts of estrogen in postmenopausal women.