ESTROGEN ENHANCES BASAL NITRIC-OXIDE RELEASE IN THE FOREARM VASCULATURE IN PERIMENOPAUSAL WOMEN

The mechanisms of estrogen-induced cardiovascular protection are incom pletely understood. Acute estrogen administration enhances acetylcholi ne-induced vasorelaxation, suggesting that endothelium-dependent facto rs may be important. The effect of long-term estrogen supplementation on endothelial function has not been well defined. In this double-blin d, randomized study, we examined endothelial function in forearm resis tance arteries in 11 perimenopausal women before and after 8 weeks of estrogen supplementation (estradiol valerate, 2 mg daily, n=6) or plac ebo (n=5). Forearm blood flow was measured by venous-occlusion plethys mography, and vasoactive agents were infused through a brachial artery cannula in doses that did not influence blood pressure or heart rate. Estrogen supplementation significantly reduced systolic and diastolic pressures but had no effect on plasma lipoproteins. Estrogen did not alter the vasodilator responses to acetylcholine at doses of 9.25, 18. 5, and 37 mu g/min (rise in forearm blood flow before estrogen: 263+/- 72%, 288+/-66%, and 383+/-84%, respectively; after estrogen: 205+/-34% , 260+/-44%, and 359+/-54%, P>.05.). Vasodilator responses to the endo thelium-independent agent sodium nitroprusside (1.6 mu g/min) were als o unchanged after estrogen supplementation. However, estrogen enhanced vasoconstrictor responses to the nitric oxide synthase inhibitor N-G- monomethyl-L-arginine at doses of 1, 2, and 4 mu mol/min (fall in fore arm blood flow before estrogen: 13+/-9%, 20+/-17%. and 26+/-8%, respec tively: after estrogen: 18+/-9%, 36+/-7%, and 47+/-7%, P=.01). Respons es to vasoactive agents were unchanged after administration of placebo . Thus. in perimenopausal women, estrogen supplementation reduces bloo d pressure and enhances basal but not acetylcholine-induced nitric oxi de release in forearm resistance arteries.