17-BETA-ESTRADIOL STIMULATES PROSTACYCLIN, BUT NOT ENDOTHELIN-1, PRODUCTION IN HUMAN VASCULAR ENDOTHELIAL-CELLS

The exact mechanisms by which estrogens protect against occlusive Vascular disorders are not known. One possibility could be an effect on vascular endothelial vasoactive compounds, such as vasodilatory prostacyclin (PGI(2)) and vasoconstrictory endothelin (ET-1). Here we report on the effect of 17 beta-estradiol on the synthesis of PGI(2) and ET-1 in cultured human umbilical vein endothelial cells. These cells were incubated in the absence (control) and presence of 17 beta-estradiol (0.001-1 mu mol/L) for 3-24 h with serum (10%) or without serum. The release of PGI,, as assessed by its metabolite 6-keto-prostaglandin F-1 alpha, and that of ET-1, were assessed by RIA. 17 beta-Estradiol (0.01-0.1 mu mol/L) predissolved in ethanol (final concentration, 0.01%) increased PGI(2) production by 26-30% in endothelial cells incubated without serum. This increase in PGI(2) production was enhanced up to 66% when 17 beta-estradiol (1 mu mol/L) was encapsulated within beta-cyclodextrin. The stimulation of PGI(2) production was detectable after 12 h of incubation. The 17 beta-estradiol-induced stimulation of PGI(2) production was blocked in dose-dependent manner by antiestrogenic tamoxifen. 17 beta-Estradiol failed to affect the production of PGI(2) if the endothelial cells were incubated with serum and had no effect on ET-1 production under any conditions. 17 beta-Estradiol-induced stimulation of vasodilatory and antiaggregatory PGI(2) production without a concomitant change in vasoconstrictory ET-1 production may provide one explanation for the ability of estradiol to maintain vascular health and protect against vascular disorders.