Endothelin converting enzyme (ECE) activity in normal pregnancy and preeclampsia

Objective: Enhanced production of endothelin-1, due to endothelial cell dysfunction has been considered to be the cause of increased plasma levels of endothelin-1 in preeclampsia. The present study was aimed at analyzing endothelin-converting-enzyme activity, (which reflect the production rate of endothelin-1 (ET-1) from big endothelin-1 (big ET-1)), big endothelin-1, and endothelin-1 concentrations from women with preeclampsia compared to normal pregnant women. Moreover, we analyzed plasma levels of these substances longitudinally throughout normal pregnancy. Study design: Twenty-nine pregnant healthy women were recruited to the study. Blood samples were obtained at 18, 28, and 38 weeks gestation and six weeks postpartum. Twenty-seven women with preeclampsia were included. Blood samples were taken at diagnosis (average 35 weeks gestation; range 27-39 weeks) and six weeks postpartum. Endothelin-1 was analyzed by enzyme linked immunoassay (ELISA) and big-ET-1 by radioimmunoassay (RIA). Endothelin-converting-enzyme activity was measured using big endothelin-1 as a substrate and thiorphan as an inhibitor of serum neutral endopeptidase. The amount of endothelin-1 generated during one hour was measured by RIA. Mean +/- SEM is given. Results: In normal pregnancy endothelin-1 concentrations at 38 weeks and postpartum were increased by 30% (p < 0.01) and 50% (p < 0.001), respectively compared with the second trimester values. Endothelin-converting-enzyme activity did not change. At diagnosis endothelin-1 was higher in women with preeclampsia than in the controls at 38 weeks (0.96 +/- 0.07 vs. 0.64 +/- 0.06 pmol/L; p < 0.001). Likewise, endothelin-converting-enzyme activity was higher in the preeclampsia group (222 15 vs. 172 +/- 8 pmol ET/ml/h; p < 0.01). This difference remained at six weeks postpartum. Conclusion: Our findings imply enhanced ET-1 production in preeclampsia. The elevated endothelin-converting-enzyme activity postpartum may indicate an inherent endothelial dysfunction predisposing to preeclampsia or that preeclampsia may cause irreversible changes in endothelial function.