In preeclampsia the increase of endothelin-binding sites in placental bed is not associated with an increase of endothelin production by placenta

Abstract

Endothelin-1 (ET) may participate in both maternal vasoconstriction and placental hypoperfusion that are present in preeclampsia (PE), but its source is unknown. In 18 primigravidae (3rd trimester), 9 of which with “pure” PE, and 9 normotensives (NT), ET in plasma was measured. We characterized pharmacologically and anatomically (by radioligand-binding and autorradiographic techniques) the ET binding sites in placental bed tissues and evaluated placental ET gene expression by RT-PCR. In PE vs. NT, higher plasma levels of NA and of ET (26.9 ± 3.3 vs. 9.4 ± 1.3 pg/ml, p < 0.05) were found. Placental bed tissues bound I-ET1 with very low Kd values. The Scatchard analyses of the results showed in PE a significant (p < 0.001) increase both of the affinity (Kd = 0.18 ± 0.03, PE vs. 0.39 ± 0.03 nM, NT) and of the density (Bmax = 78.60 ± 1.40, PE vs. 63.30 ± 1.70 fmol/mg tissue, NT) of ET binding site which was confirmed in autoradiography studies (higher silver grain density in the intima of the spiral arteries walls and in the myometrium of PE v NT). However, relative ET-mRNA levels respectively in central and peripheral areas of placenta were similar (p > 0.40) in NT (0.56 ± 0.16 and 0.77 ± 0.09) and in PE (0.48 ± 0.10 and 0.74 ± 0.13). We conclude that in PE the placenta may not be the main source of the increased maternal circulating levels of ET. Meanwhile, ET high plasma levels along with the increased density and affinity of ET-binding sites in placental bed, may participate in the utero-placental hypoperfusion of PE. Supported by PRAXIS XXI SAU 1302/95.