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 A(2) are involv ed in the pathophysiology of gestational hypertension and preeclampsia. STUDY DESIGN: In a longitudinal design, venous blood samples and 24-hour ur ine specimens were collected from 396 women in each trimester of pregnancy. After delivery of all patients, Venous plasma endothelin was assessed in 2 0 subjects with identified preeclampsia, 48 subjects with gestational hyper tension, and 59 normotensive subjects. Urinary excretions of the thromboxan e A(2) and of the prostacyclin metabolites thromboxane B-2 and 6-keto-prost aglandin F-1 alpha were assessed in 16 subjects with preeclampsia, 35 subje cts 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 excr etion of thromboxane B-2 and that of 6-keto-prostaglandin F-1 alpha (P <.00 1). The overall thromboxane B-2 and 6-keto-prostaglandin F-1 alpha urinary excretions increased throughout pregnancy and the overall thromboxane B-2/6 -keto-prostaglandin F-1 alpha ratio decreased. No significant differences i n endothelin, thromboxane B-2, and 6-keto-prostaglandin F-1 alpha excretion levels or in thromboxane B-2/6-keto-prostaglandin F-1 alpha ratios were fo und between women with preeclampsia, gestational hypertension, and normoten sion. Only in a small group of patients with severe preeclampsia (n = 2) an d severe gestational hypertension (n = 2) were increased second-trimester e ndothelin Values and increased thromboxane B-2/6-keto-prostaglandin F-1 alp ha ratios found. CONCLUSION: In this longitudinal study we found no evidence for prostacycli n deficiency or increased endothelin levels in preeclampsia. Only women wit h severe preeclampsia and severe gestational hypertension expressed increas ed endothelin levels and thromboxane dominance over prostacyclin.