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 oophorectomized female pigs was determined by thymidine incorporation in the absence and presence of endothelin-1 with and without 17beta-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 beta-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.