Background At physiological concentrations, 17β-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 N^G-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.