Endothelin system in normal and hypertensive pregnancy

Pre-eclampsia complicates approximately 5-7% of pregnancies and it may be deleterious to both maternal and fetal health. In a prospective study, we investigated plasma endothelin (ET)-1 concentration within the 24th and 36th gestational week in non-smoking pregnant women. Thirty women fulfilled the criteria for the diagnosis of pre-eclampsia according to the American College of Obstetricians and Gynaecologists: de novo arterial hypertension after the 20th gestational week in at least two separate measurements and proteinuria of more than 300 mg/l in a random specimen. For comparison, we analysed blood samples from 125 non-pre-eclamptic pregnant women. ET-1 concentrations were higher in pre-eclamptic pregnancies at both time points (mean+/-S.D.: 1.07+/-2.00 versus 0.54+/-0.56 pg/ml, P=0.045 at 24th week; 0.75+/-1.20 versus 0.44+/-0.45 pg/ml, P=0.023 at 36th week). Receiver operating characteristic (ROC) curves revealed a significant interaction between ET-1 plasma concentrations at the 36th week and the diagnosis of pre-eclampsia [area under the curve (AUC)+/-S.E.M.: 0.657+/-0.049, P=0.008] and a cut-off value at 0.30 pg/ml. Multivariate analysis showed a 4.6-fold higher chance (95% confidence interval: 1.7-12.1, P=0.002) for the diagnosis of pre-eclampsia in pregnant women with ET-1 plasma concentration higher than 0.30 pg/ml at the 36th week. Interaction between ET-1 plasma concentration at the 24th week and diagnosis of pre-eclampsia was not significant in ROC curve analysis (AUC+/-S.E.M.: 0.594+/-0.071, P=0.278). Interestingly, we found a strong positive correlation between ET-1 concentration in the 24th and 36th week in linear regression analysis in pre-eclamptic (r=0.99, P<0.001) and non-pre-eclamptic pregnancies (r=0.61, P<0.001) with a slightly, non-significant decrease from the 24th to 36th week (for group means see above), indicating individual plasma ET-1 levels even in non-pre-eclamptic pregnancies. Linear regression analysis showed no correlation between blood pressure or urine protein excretion and ET-1 plasma concentration in non-pre-eclamptic pregnant women. In conclusion, our prospective study indicates that the ET system is, in contrast to most other forms of human hypertension, activated in pre-eclamptic pregnant women.