(Circulation. 1997;96:2795-2801.)
© 1997 American Heart Association, Inc.
Articles |
The Role of Nitric Oxide in Coronary Vascular Effects of Estrogen in Postmenopausal Women
From the Cardiology Branch and Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
Correspondence to Dr Richard O. Cannon III, National Institutes of Health, Bldg 10, Room 7B15, 10 Center Dr MSC1650, Bethesda, MD 20892-1650.
Background At physiological concentrations, 17ß-estradiol selectively enhances endothelium-dependent coronary vasodilation by an unknown mechanism in postmenopausal women.
Methods and Results To assess the contribution of nitric oxide (NO) to the vascular effects of estradiol, we measured coronary epicardial and microvascular responses to intracoronary acetylcholine (range, 3 to 300 µg/min for 2 minutes) before and after intracoronary estradiol 75 ng/min for 15 minutes in 20 estrogen-deficient women, 16 of whom had angiographic evidence of atherosclerosis or risk factors for atherosclerosis. This testing was repeated after inhibition of NO synthesis with intracoronary NG-monomethyl-L-arginine (L-NMMA) 64 µmol/min for 5 minutes. Estradiol increased acetylcholine-stimulated coronary flow from 54±48% (mean±SD) above baseline values before estradiol infusion to 100±63% above baseline values (P=.007) and decreased coronary resistance from 32±21% to 46±15% below baseline values (P=.007) at a coronary sinus estradiol concentration of 1725±705 pmol/L (470±192 pg/mL). Estradiol also tended to lessen the severity of acetylcholine-induced epicardial coronary artery vasoconstriction from 8±11% to 3±11% below baseline values (P=.123). However, during L-NMMA infusion, estradiol no longer potentiated the effects of acetylcholine on coronary flow dynamics; coronary flow increased 39±46% above baseline values and coronary resistance decreased 19±30% below baseline values (both P<.001 versus pre–L-NMMA responses). The epicardial diameter decreased 8±11% below baseline values (P=.06 versus pre–L-NMMA response).
Conclusions The effects of estradiol at physiological concentrations on endothelium-dependent coronary vasodilator responsiveness in postmenopausal women are mediated by enhanced bioavailability of NO, which may be responsible in part for the cardioprotective effects of estrogen.
Key Words: atherosclerosis • coronary disease • nitric oxide • endothelium • hormones
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