ENDOTHELIN-1-LIKE IMMUNOREACTIVITY AND ENDOTHELIN RECEPTORS IN THE HUMAN PLACENTA FROM NORMOTENSIVE AND HYPERTENSIVE PREGNANCIES

The levels of endothelin-1-like immunoreactivity (ET-1-LI) and charact eristics of endothelin receptors in the chorionic villous tissue of hu man placenta were determined. The ET-1-LI level in chorionic villous t issue obtained from normal term placenta was 2,450 +/- 940 pg/g wet we ight (mean +/- SD, n = 4). Further analysis using gel permeation chrom atography and reverse-phase high performance liquid chromatography sho wed that the main ET-1-LI constituent of ET-1-LI in this tissue was ET -1. Scatchard analysis of [I-125]ET-1 binding to the membrane fraction of chorionic villous tissue obtained from term placenta showed high a ffinity receptor sites with an apparent dissociation constant (Kd) of 23.6 +/- 11.1 pM and a Bmax value of 388 +/- 238 fmol/mg protein (n = 5). The same binding study with [I-125]ET-3 showed a Kd of 13.9 +/- 3. 8 pM and a Bmax value of 176 +/- 78 fmol/mg protein (n = 5). These res ults suggest that both ET-A and ET-B receptors (ET-AR and ET-BR) are e xpressed in chorionic villous tissue. This finding was further confirm ed by Northern blot analysis showing the expression of both ET-AR and ET-BR mRNAs in this tissue. ET-1-LI in the umbilical venous plasma of the newborns from women with pregnancy-induced hypertension (PIH) (38. 3 +/- 10.4 pg/mL, n = 5) was significantly (P < 0.05) higher than that in the normal newborns from normotensive pregnant women (26.3 +/- 5.2 pg/mL, n = 12). However, in placental chorionic villous tissue obtain ed from PIH women, both ET-1-LI level and ET binding profile were not different from those in chorionic villous tissue from normotensive pre gnant women. These results suggest that the abundant ET-ET receptor sy stem is present in the placental chorionic villous tissue and that thi s system is not the major factor of the pathogenesis of placental dysf unction occurring in PIH because these systems are similar in normoten sive and hypertensive pregnancies.