ASSOCIATION OF CIRCULATING ENDOTHELIN AND NORADRENALINE WITH INCREASED CALCIUM-CHANNEL BINDING-SITES IN THE PLACENTAL BED IN PREECLAMPSIA

Objective To evaluate factors contributing to both placental hypoperfu sion and maternal vasoconstriction in pre-eclampsia. Design Single cen tre, comparative study of calcium-channel density and affinity in the placental bed of pregnant women with normotension and pre-eclampsia. S etting Teaching hospital. Participants Twenty-two primigravidae in the third trimester of pregnancy: 10 with pre-eclampsia and 12 normotensi ve. Methods Plasma levels of endothelin-1 (by RIA) and noradrenaline ( by HPLC-ED) were measured. Both pharmacological characterisation and a natomical localisation of dihydropyridine-sensitive binding sites (usi ng radioligand-binding studies and autorradiographic techniques) were determined with 3H-isradipine in placental bed tissues to determine bo th the density (Bmax) and the affinity (Kd) of receptor sites. Results Higher plasma levels of endothelin-1 and noradrenalin were found in w omen with preeclampsia compared with normotensive women. Placental bed tissues bound 3H-isradipine in a saturable, reversible time and tempe rature-dependent manner with very low Kd values. Study of the 3H-israd ipine specificity binding included the use of several dihydropyridine displacers. In the group with pre-eclampsia the Scatchard analysis of the results showed a significant increase (P < 0.001) both in the affi nity [Kd = 0.23 nmol (0.04) vs 0 45 nmol (0.03), pre-eclampsia vs norm otensive] and in the density of calcium-channel binding sites [Bmax = 77.70 fmol/mg (1.30) vs 64.30 fmol/mg (1.80) tissue, pre-eclampsia vs normotensive]. Autoradiography confirmed that in the placental bed tis sue of those with pre-eclampsia there was a much higher silver grain d ensity in the arteries walls, compared with normotensive women. Conclu sions In pre-eclampsia there is an increase in the maternal circulatio n of two strong vasoconstrictor factors (endothelin-1 and noradrenalin ) and a sharp increase both in the density and the affinity of calcium -channel binding sites in placental bed central area. The latter may s trongly contribute to the perpetuation of the uteroplacental hypoperfu sion either by itself or by amplifying the local actions of circulatin g factors, such as endothelin-l and noradrenalin.