Objectives. This experiment sought to determine the effect of short-term administration of estrogen on endothelium-dependent dilation in the coronary arteries of 13 surgically postmenopausal female cynomolgus monkeys.

Background. Long-term estrogen replacement therapy prevents impaired endothelium-dependent dilation of atherosclerotic coronary arteries in postmenopausal female monkeys. However, it remains unclear whether this action of estrogen is due to long-term effects on plasma lipids and atherogenesis or to direct short-term effects on the endothelium.

Methods. The monkeys consumed an atherogenic diet for 18 months after bilateral ovariectomy. Vascular responses were measured just before euthanasia and necropsy. Dextrose in water (control), acetylcholine, 10⁻⁶M, and nitroglycerin were infused for 2.5 min each both before and 20 min after intravenous injection of 54 ng ethinyl estradiol.

Results. Quantitative coronary angiography revealed that the arteries constricted (−17 ± 3%) in response to intracoronary infusion of acetylcholine before estrogen treatment but dilated (+ 5 ± 3%) 20 min after intravenous injection of ethinyl estradiol (p < 0.05). Coronary arteries dilated in response to nitroglycerin both before and after administration of estrogen (p > 0.05). Vascular responses of coronary arteries, both before and after administration of estrogen, were not associated with variation in plasma lipid concentrations, blood pressure, heart rate or plaque size.

Conclusions. Estrogen affects endothelium-dependent coronary dilation within 20 min of administration and may have rapid direct effects on the vascular endothelium.