17β-estradiol preserves endothelial vasodilator function and limits low-density lipoprotein oxidation in hypercholesterolemic swine

Abstract

Background: Cardiovascular events are less prevalent in premenopausal women and women receiving estrogen replacement than in postmenopausal women or men. Endotheliumderived relaxing factor (EDRF) is an important local modulator of vascular tone, and abnormal endothelial function is related, in part, to the oxidative modification of low-density lipoprotein (LDL). Estrogens possess substantial antioxidant activity and inhibit LDL modification in vitro. Methods and Results: We investigated the effects of 17β-estradiol (E2) on endothelial vasomotor function in cholesterol-fed miniature swine. Animals underwent ovariectomy or a sham procedure and received E2 or placebo via implant yielding three groups: sham, ovariectomy (E2 placebo), and implant (E2 implant). After 16 weeks, coronary arteries were harvested and endothelial function was examined in vitro. Vessels from the sham and implant groups demonstrated preserved endothelium-dependent relaxation to bradykinin, substance P, and A23187. Vessels from the ovariectomy group exhibited impaired relaxation to bradykinin and substance P (P