Vasoactive mediators in pregnancy-induced hypertensive disorders: a longitudinal study.
OBJECTIVE
The objective of this study was to evaluate the extent to which endothelin and the eicosanoids prostacyclin and thromboxane A2 are involved in the pathophysiology of gestational hypertension and preeclampsia.


METHODS
In a longitudinal design, venous blood samples and 24-hour urine specimens were collected from 396 women in each trimester of pregnancy. After delivery of all patients, venous plasma endothelin was assessed in 20 subjects with identified preeclampsia, 48 subjects with gestational hypertension, and 59 normotensive subjects. Urinary excretions of the thromboxane A2 and of the prostacyclin metabolites thromboxane B2 and 6-keto-prostaglandin F1 alpha were assessed in 16 subjects with preeclampsia, 35 subjects with gestational hypertension, and 31 normotensive subjects.


RESULTS
Endothelin levels showed a second-trimester drop in all groups. In all 3 gestational trimesters a high correlation was found between the excretion of thromboxane B2 and that of 6-keto-prostaglandin F1 alpha (P <.001). The overall thromboxane B2 and 6-keto-prostaglandin F1 alpha urinary excretions increased throughout pregnancy and the overall thromboxane B2 /6-keto-prostaglandin F1 alpha ratio decreased. No significant differences in endothelin, thromboxane B2, and 6-keto-prostaglandin F1 alpha excretion levels or in thromboxane B2 /6-keto-prostaglandin F1 alpha ratios were found between women with preeclampsia, gestational hypertension, and normotension. Only in a small group of patients with severe preeclampsia (n = 2) and severe gestational hypertension (n = 2) were increased second-trimester endothelin values and increased thromboxane B2 /6-keto-prostaglandin F1 alpha ratios found.


CONCLUSIONS
In this longitudinal study we found no evidence for prostacyclin deficiency or increased endothelin levels in preeclampsia. Only women with severe preeclampsia and severe gestational hypertension expressed increased endothelin levels and thromboxane dominance over prostacyclin.
Paarlberg
K M
KM
Division of Maternal-Fetal Medicine and Prenatal Diagnosis, Department of Obstetrics and Gynecology, Free University Hospital Amsterdam, The Netherlands.
de Jong
C L
CL
van Geijn
H P
HP
van Kamp
G J
GJ
Heinen
A G
AG
Dekker
G A
GA
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000328:Adult; D015777:Eicosanoids / Q000652:urine*; D016232:Endothelins / Q000097:blood*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008137:Longitudinal Studies; D011225:Pre-Eclampsia / Q000097:blood / Q000378:metabolism* / Q000652:urine; D011247:Pregnancy / Q000097:blood / Q000652:urine; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood / Q000378:metabolism* / Q000652:urine; D012016:Reference Values; D013928:Thromboxane A2 / Q000652:urine; D013929:Thromboxane B2 / Q000652:urine
D015777:Eicosanoids; D016232:Endothelins; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha