V Guetta1, A A Quyyumi, A Prasad, J A Panza, M Waclawiw, R O Cannon. 1. Cardiology Branch and Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md 20892-1650, USA.
Abstract
BACKGROUND: At physiological concentrations, 17beta-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 microg/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 N(G)-monomethyl-L-arginine (L-NMMA) 64 micromol/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.
BACKGROUND: At physiological concentrations, 17beta-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 microg/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 N(G)-monomethyl-L-arginine (L-NMMA) 64 micromol/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.
Authors: Matthew D Muller; Zhaohui Gao; Jessica L Mast; Cheryl A Blaha; Rachel C Drew; Urs A Leuenberger; Lawrence I Sinoway Journal: Am J Physiol Heart Circ Physiol Date: 2012-02-17 Impact factor: 4.733
Authors: R H Karas; J B Hodgin; M Kwoun; J H Krege; M Aronovitz; W Mackey; J A Gustafsson; K S Korach; O Smithies; M E Mendelsohn Journal: Proc Natl Acad Sci U S A Date: 1999-12-21 Impact factor: 11.205
Authors: B Deodato; D Altavilla; G Squadrito; G M Campo; M Arlotta; L Minutoli; A Saitta; D Cucinotta; G Calapai; A P Caputi; M Miano; F Squadrito Journal: Br J Pharmacol Date: 1999-12 Impact factor: 8.739
Authors: Andrew Sherwood; Sat Byul Park; Joel W Hughes; James A Blumenthal; Alan Hinderliter; Ranak Trivedi; Judith McFetridge-Durdle Journal: Menopause Date: 2010-03 Impact factor: 2.953
Authors: Jordan M Glenn; Michelle Gray; Lauren N Wethington; Matthew S Stone; Rodger W Stewart; Nicole E Moyen Journal: Eur J Nutr Date: 2015-12-11 Impact factor: 5.614