Endothelial vasoactive mediators in preeclampsia

Abstract

Objective: In recent years an increasing amount of evidence supports the concept that preeclampsia is an endothelial disease. The purpose of our study was to evaluate the extent to which endothelial cell dysfunction is involved in pathophysiology of preeclampsia.

Study design: We studied the urinary excretion of thromboxane B2 and 6-keto-prostaglandin F1 alpha and the venous plasma endothelin levels in 23 preeclamptic patients and in control subjects. In six of these patients and in six controls arterial plasma endothelin levels were also measured. In addition, plasma levels of calcitonin gene-related peptide and plasma fibronectin levels were measured. Results were analyzed by Wilcoxon's rank-sum test or signed-rank test.

Results: In preeclampsia the urinary thromboxane B2/6-keto-prostaglandin F1 alpha ratio (p < 0.001), venous plasma endothelin levels (p < 0.001), and plasma fibronectin levels (p < 0.001) were significantly elevated compared with normotensive pregnancy. Arterial plasma endothelin levels were significantly higher than venous plasma endothelin levels in normotensive and hypertensive patients (p < 0.05). Calcitonin gene-related peptide levels showed a wide range in normotensive pregnancy and in preeclampsia, but the difference was not significant.

Conclusions: These results confirm the extensive involvement of the endothelium in the pathophysiology of preeclampsia. Preeclamptic vasoconstriction seems to be mediated by an increase in the vasoconstrictor autocoids thromboxane A2 and endothelin. Production of prostacyclin by the vessel wall and endovascular trophoblast might be just a pivotal escape mechanism of the uteroplacental circulation. Calcitonin gene-related peptide appears not to be involved in the pathophysiology of preeclampsia.