Mechanism of endothelin-1 release from endothelial cells in pregnancy-induced hypertension.

We investigated the mechanism of vasoconstrictor-induced endothelin-1 (ET-1) release from human umbilical vein endothelial cells (HUVECs) in serum from women with pregnancy-induced hypertension (PIH). We obtained serum samples from seven women with PIH, seven healthy nonpregnant women (NP), and seven normal pregnant women (NPIH). ET-1 and inositol 1,4,5-trisphosphate (IP3) were assayed by ET-1 ELISA and an IP3 3H assay system, respectively. ET-1 release from HUVECs incubated with 10% serum (NP, NPIH, and PIH) was greater than that without human serum. Angiotensin II (Ang II)- and epinephrine (Epi)-induced ET-1 release were significantly increased by PIH serum. IP3 production in HUVECs incubated with 10% serum (NP, NPIH, and PIH) was greater than that without human serum. Ang II- or Epi-induced IP3 production in HUVECs incubated with PIH serum was increased but not significantly compared to that with other sera. Our results suggest that increased ET-1 release from HUVECs incubated with human serum may be mediated by IP3 production, but that Ang II- or Epi-induced ET-1 release from HUVECs incubated with PIH serum may be mediated by another mechanism.