The role of arachidonic acid metabolites in preeclampsia

Preeclampsia is characterized by imbalances in the production rates of several arachidonic acid metabolites. There is a considerable amount of evidence to indicate that PGI2 production is decreased in preeclampsia. PGI2 is a potent vasodilator, an inhibitor of platelet aggregation, and an inhibitor of uterine contractility. Evidence is accumulating that TX production in preeclampsia is either increased or unchanged so that the ratio of TX to PGI2 favors TX. TX opposes the actions of PGI2 in that it is a potent vasoconstrictor, a stimulator of platelet aggregation, and a stimulator of uterine contractility. Therefore, an imbalance of increased TX/decreased PGI2 production can account for the major clinical symptoms of preeclampsia. There is now preliminary evidence that the placenta produces lipoxygenase, as well as cyclooxygenase compounds. The hydroxyeicosatetranoic acids (5-HETE, 12-HETE, 15-HETE) and LTB4 have been identified as placental products. The preeclamptic placenta appears to be deficient in the 5- and 12-lipoxygenase enzymes, as indicated by placental production of 5-HETE and 12-HETE. Little is known about the regulation of arachidonic acid metabolites in normal or preeclamptic pregnancies. Steroids are known to affect cyclooxygenase product production. Progesterone, for example, inhibits PGI2 production. Although circulating and urinary concentrations of progesterone do not differ between normal and preeclamptic pregnancies, there is one report that placental progesterone concentrations are higher in preeclampsia; this may partially explain the decreased placental production of PGI2. There is a considerable amount of evidence in various tissues that regulatory interactions exist between the cyclooxygenase and lipoxygenase metabolites of arachidonic acid, but the role of these interactions in preeclampsia is not known. There is still much to be learned about the etiology of preeclampsia, but it is certain that aberrations in the production of arachidonic acid metabolites play an important role. It is likely that the effective treatment of preeclampsia will come from understanding the regulation of the arachidonic acid metabolites during pregnancy, and, therefore, the ability to specifically treat the production imbalances that characterize this disorder.