THE ROLE OF NITRIC-OXIDE IN CORONARY VASCULAR EFFECTS OF ESTROGEN IN POSTMENOPAUSAL WOMEN

Background At physiological concentrations, 17 beta-estradiol selectiv ely 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 intra coronary acetylcholine (range, 3 to 300 mu g/min for 2 minutes) before and after intracoronary estradiol 75 ng/min for 15 minutes in 20 estr ogen-deficient women, 16 of whom had angiographic evidence of atherosc lerosis or risk factors for atherosclerosis. This testing was repealed after inhibition of NO synthesis with intracoronary N-G-monomethyl-L- arginine (L-NMMA) 64 mu mol/min for 5 minutes. Estradiol increased ace tylcholine-stimulated coronary flow from 54+/-48% (mean+/-SD) above ba seline values before estradiol infusion to 100-63% above baseline valu es (P=.007) and decreased coronary resistance from 32+/-21% to 46+/-15 % below baseline values (P=.007) at a coronary sinus estradiol concent ration of 1725+/-705 pmol/L (470+/-192 pg/mL). Estradiol also tended t o lessen the severity of acetylcholine-induced epicardial coronary art ery vasoconstriction from 8+/-11% to 3+/-11% below baseline values (P= .123). However, during L-NMMA infusion, estradiol no longer potentiate d the effects of acetylcholine on coronary flow dynamics; coronary flo w increased 39+/-46% above baseline values and coronary resistance dec reased 19+/-30% below baseline values (both P<.001 versus pre-L-NMMA r esponses). The epicardial diameter decreased 8+/-11% below baseline va lues (P=.06 versus pre-L-NMMA response). Conclusions The effects of es tradiol at physiological concentrations on endothelium-dependent coron ary vasodilator responsiveness in postmenopausal women are mediated by enhanced bioavailability of NO, which may be responsible in part for the cardioprotective effects of estrogen.