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(Circulation. 2000;102:1617.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

17ß-Estradiol Decreases Endothelin-1 Levels in the Coronary Circulation of Postmenopausal Women With Coronary Artery Disease

Carolyn M. Webb, PhD; Mohammad A. Ghatei, PhD; John G. McNeill; DCRR; Peter Collins, MD, FRCP

From Cardiac Medicine (C.M.W., J.G.M., P.C.), National Heart & Lung Institute, Imperial College School of Medicine, and Royal Brompton Hospital, and Department of Metabolic Medicine (M.A.G.), Hammersmith Hospital, London, UK.

Correspondence to Dr Peter Collins, Cardiac Medicine, National Heart & Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, UK. E-mail peter.collins{at}ic.ac.uk

Background—Estrogen reverses acetylcholine-induced coronary vasoconstriction via the possible facilitation of endothelium-derived NO. Estrogen also affects endothelium-derived constrictor factors. We therefore investigated the effects of 17ß-estradiol on coronary vasomotor responses to substance P (SP), and coronary sinus endothelin-1 and NO metabolite levels in postmenopausal women with coronary heart disease.

Methods and Results—We studied 20 women; 14 received estrogen (mean age 65±2 years) and 6 served as ethanol control subjects (age 63±3 years). Intracoronary infusions of papaverine (8 mg) and SP were administered before and 20 minutes after 50 pg/min 17ß-estradiol or 0.2 µL/min control. Coronary blood flow was calculated from the diameter, as measured with quantitative coronary angiography, and flow velocity, as measured with intracoronary Doppler. Coronary sinus plasma endothelin-1 and nitrite/nitrate (NO₂/NO₃) were measured at baseline, at peak velocity response to each infusion, and every 5 minutes during the estradiol infusion. Endothelin-1 levels were decreased after 20 minutes of estradiol (1.12±0.18 versus 0.86±0.17 pmol/L baseline2 versus estradiol, P=0.05). Endothelin-1 levels to SP decreased after 17ß-estradiol (1.29±0.18 versus 1.04±0.15 and 1.3±0.16 versus 0.99±0.17 pmol/L for before versus after estradiol, 10 and 25 pmol/min SP; both P<0.05). NO₂/NO₃ levels did not change. There was no change in vasomotor responses to estradiol alone or to papaverine or SP before versus after estradiol.

Conclusions—Short-term intracoronary 17ß-estradiol administration decreases coronary endothelin-1 levels. There was no enhancement of vasomotor responses to SP after the administration of estrogen, suggesting that the effects of estrogen on coronary acetylcholine responses may be a specific and not a generalized effect on coronary vasoreactivity.

Key Words: estrogen • arteries • endothelium • endothelin-1 • nitric oxide

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