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 proliferation of vascular smooth muscle and has been implicated in the development of atherosclerosis. Estrogen modulates production of and contractile responses to endothelin-1. Since atherosclerosis is less in estrogen-replete women compared to men, experiments were designed to determine whether or not there were gender-associated differences in proliferative responses to endothelin-1 and effect of estrogen status on those responses. Proliferation of smooth muscle cells derived from coronary arteries of sexually mature, gondally intact male and female and oophorect-omized female pigs was determined by thymidine incorporation in the absence and presence of endothelin-1 with and without 17β-estradiol. Endothelin-1 (10-9 M to 10-7 M) significantly inhibited proliferation only in coronary smooth muscle cells from intact female pigs. Addition of β-estradiol inhibited proliferation of cells from intact females but there was not a synergistic effect with endothelin-1. Gender associated inhibition of smooth muscle proliferation by endothelin-1 may contribute, in part, to cardioprotection noted in estrogen-replete states.