Circulation, Vol 89, 52-60, Copyright © 1994 by American Heart Association
SE Reis, ST Gloth, RS Blumenthal, JR Resar, HA Zacur, G Gerstenblith and JA Brinker
BACKGROUND: Estrogen administration in postmenopausal women is associated
with a 50% reduction in the clinical manifestations of coronary artery
disease. The mechanisms are not known, although one potential explanation
is estrogen-induced modulation of coronary vasoreactivity. Acetylcholine is
an endothelium-dependent vasodilator that may be used to assess coronary
vasoreactivity and elicits coronary responses that parallel those found
with common daily vasomotor stimuli. Therefore, we tested whether estrogen
attenuates abnormal coronary vasomotor responses to acetylcholine in
postmenopausal women. METHODS AND RESULTS: Acetylcholine-induced changes in
coronary flow, resistance, and cross-sectional area were determined before
and 15 minutes after intravenous administration of ethinyl estradiol (EE,
35 micrograms) in 15 postmenopausal women. The influence of estrogen on
basal coronary flow, resistance, and epicardial cross-sectional area was
also assessed by measuring these parameters before and after EE or placebo
administration in 33 women. Estrogen altered basal coronary vasomotor tone
in 22 women as manifested by an EE-induced 23.3 +/- 4.5% (mean +/- SEM)
increase (P < .01) in coronary 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 administration in 11 women did not change
these parameters. Estrogen also attenuated abnormal coronary vasomotor
responses to acetylcholine. Seven women who exhibited a paradoxical
acetylcholine-induced decrease in coronary flow (-33.5 +/- 12.3%, P <
.01) and increase in resistance (38.9 +/- 14.1%, P = .05) and seven who had
an abnormal acetylcholine-induced decrease in epicardial cross-sectional
area (-14.2 +/- 4.4%; P = .04) did not have acetylcholine-induced changes
in these parameters after EE administration. 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 acetylcholine were not affected by EE
administration. CONCLUSIONS: EE attenuates abnormal coronary vasomotor
responses to acetylcholine in postmenopausal women. EE also decreases basal
coronary vasomotor tone as manifested by increased coronary flow, decreased
resistance, and increased epicardial cross-sectional area. These acute
effects of estrogen on coronary vasoreactivity may explain, in part, the
cardioprotective effects of estrogen in postmenopausal women.
ARTICLES
Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women
Department of Medicine, Johns Hopkins University, Baltimore, Md.
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