Gender-related differences in proliferative responses of vascular smooth muscle cells to endothelin-1

Endothelin-1 is an endothelium-derived factor which alters tone and prolife ration of vascular smooth muscle and has been implicated in the development of atherosclerosis. Estrogen modulates production of and contractile respo nses to endothelin-1. Since atherosclerosis is less in estrogen-replete wom en compared to men, experiments were designed to determine whether or not t here were gender-associated differences in proliferative responses to endot helin-1 and effect of estrogen status on those responses. Proliferation of smooth muscle cells derived from coronary arteries of sexually mature, gond ally intact male and female and oophorectomized female pigs was determined by thymidine incorporation in the absence and presence of endothelin-1 with and without 17 beta -estradiol. Endothelin-1 (10(-9) M to 10(-7) M) signif icantly inhibited proliferation only in coronary smooth muscle cells from i ntact female pigs. Addition of beta -estradiol inhibited proliferation of c ells from intact females but there was not a synergistic effect with endoth elin-1. Gender associated inhibition of smooth muscle proliferation by endo thelin-1 may contribute, in part, to cardioprotection noted in estrogen-rep lete states.