Although estrogen replacement therapy has been associated with reduction of cardiovascular events in postmeno-pausal women (PMW), the underlying mechanisms are pooly understood. Because the beneficial effect of estrogen on vasomotor function and production of vasoconstrictive endothelin-1 may be a mechanism by which cardiovascular disease events are reduced, we accessed the acute effect of estrogen on endothelial dependent, independent vasodilaton and plasma endothelin-1 level and investigated whether the acute effect of estrogen on vascular response is related to reduced circulating plasma endothelin-1 level.

The diameter of the brachial artery at rest, during reactive hyperemia (FMV) and to response to nitroglycerine (NMV) were measured using high resolution ultrasound. Twenty-one PMW, 523 years old, 8 of whom had hypercholesterolemia were included and randomized to receive placebo, conjugated estrogen 2.5 mg and 5.0 mg with one week between each investigation. FMV and plasma endothelin-1 were assessed before and 30 minutes after iv administration of each substance. Sublingual nitroglycerine (NG) was given at the end of each investigation and NMV was measured.

FMV and plasma endothelin-1 were not changed after placebo administration. FMV increased sinigicantly only after administration of CE 5.0 mg in healhy PMW and both after administration of CE 2.5 and 5.0 mg in PMW with hypercholesterolemia. NG induced more significant vasodilation after administration of estrogen than placebo in only PMW with hypercholesterolemia. Plasma endothelin-1 level decreased significantly after administration of CE 5.0 mg in PMW with hypercholesterolemia. We could not find direct correlation between increase of FMV and decrease of plasma endothelin-1 level.

IV administration of conjugated estrogen improves endothelium-dependent vasodilation in PMW and may improve endothelium-independent vasodilation in PMW with hypercholesterolemia. These finding may be partly originated by reduced plasma endothelin-1 level after estrogen administration.