Se. Reis et al., ETHINYL ESTRADIOL ACUTELY ATTENUATES ABNORMAL CORONARY VASOMOTOR RESPONSES TO ACETYLCHOLINE IN POSTMENOPAUSAL WOMEN, Circulation, 89(1), 1994, pp. 52-60
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.