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

The exact mechanisms by which estrogens protect against occlusive Vasc ular disorders are not known. One possibility could be an effect on va scular endothelial vasoactive compounds, such as vasodilatory prostacy clin (PGI(2)) and vasoconstrictory endothelin (ET-1). Here we report o n 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 i ncubated 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 rel ease of PGI,, as assessed by its metabolite 6-keto-prostaglandin F-1 a lpha, 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%) inc reased PGI(2) production by 26-30% in endothelial cells incubated with out serum. This increase in PGI(2) production was enhanced up to 66% w hen 17 beta-estradiol (1 mu mol/L) was encapsulated within beta-cyclod extrin. The stimulation of PGI(2) production was detectable after 12 h of incubation. The 17 beta-estradiol-induced stimulation of PGI(2) pr oduction was blocked in dose-dependent manner by antiestrogenic tamoxi fen. 17 beta-Estradiol failed to affect the production of PGI(2) if th e endothelial cells were incubated with serum and had no effect on ET- 1 production under any conditions. 17 beta-Estradiol-induced stimulati on of vasodilatory and antiaggregatory PGI(2) production without a con comitant change in vasoconstrictory ET-1 production may provide one ex planation for the ability of estradiol to maintain vascular health and protect against vascular disorders.