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.


METHODS
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.


CONCLUSIONS
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.
Department of Obstetrics and Gynaecology, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden. gunilla.ajne@hs.se
Gunilla
G
Ajne
Kerstin
K
Wolff
Frej
F
Fyhrquist
Kjell
K
Carlström
Anette
A
Hemsén-Mörtberg
Henry
H
Nisell
D000328:Adult; D016282:Aspartic Acid Endopeptidases / Q000097:blood / Q000378:metabolism*; D019332:Endothelin-1 / Q000097:blood / Q000378:metabolism*; D000072396:Endothelin-Converting Enzymes; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D008666:Metalloendopeptidases; D011225:Pre-Eclampsia / Q000097:blood / Q000378:metabolism*; D011247:Pregnancy
D019332:Endothelin-1; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes