The factors that regulate the synthesis and release of renin by human decidua and other extrarenal tissues are poorly understood. Recent studies have demonstrated that the potent vasoconstrictive peptide endothelin (ET) inhibits the release of renin from renal juxtaglomerular cells, probably by a calcium-dependent mechanism. To determine whether ET also influences the release of renin from decidual tissue, we have examined the effects of ET on the synthesis and release of renin by primary cultures of human decidual cells. Decidual cells exposed continuously to ET (10(-7) mol/L) for 96 h released significantly more renin than control cells. At 48, 72, and 96 h, the ET-exposed cells released 284, 645, and 1300% more renin, respectively, than control cells. Greater than 95% of the renin released into the medium was in the form of prorenin, the precursor of renin. The stimulation by ET was dose-dependent, with half-maximal stimulation at a concentration of 7 x 10(-9) mol/L. ET-2 and ET-3, as well as the precursor to ET (big ET), also stimulated renin release. The total amount of renin in the media and cells of ET-exposed decidual cells was significantly greater than that of control cells, indicating that the increase in renin release was accompanied by an increase in synthesis. In addition, Northern blot analysis of total RNA from cells exposed for 96 h to ET-1 (10(-7) mol/L) indicated that the renin messenger RNA content of ET-1-exposed cells was approximately 100 times greater than that of control cells. These results indicate that ET is a potent stimulus to the synthesis and release of prorenin from human decidua and that the effect of ET on decidual renin expression is opposite to that observed for the expression of renal renin.