12-hydroxy-5-8-10-14-eicosatetraenoic-acid and Pre-Eclampsia

The important role of eicosanoids in pregnancy-induced hypertension is generally accepted. Because of the lack of innervation of the uteroplacental vessels, humoral vasoactive factors are important for the regulation of vascular tone. Until now, mainly the balance of vasodilatative and vasoconstrictive prostaglandins has been studied. We were able to confirm their intrauterine imbalance in hypertensive pregnancies. In addition, the placental production of less known lipoxygenase metabolites has been analyzed in this study. Intrauterine tissues (30-100mg wet weight) were examined for their release of eicosanoids. Short term tissue cultures were performed in Hanks balanced salts solution (HBSS) at 37 degrees C in an atmosphere of 95% air/5% CO2 with and without incorporation of tritiated arachidonic acid. The arachidonate metabolites in culture media were analyzed by High Performance Liquid Chromatography (HPLC) with radioactivity detection or by enzyme immunoassays or radioimmunoassays, respectively. All intrauterine tissues released more lipoxygenase metabolites than cyclooxygenase metabolites with 12-hydroxy-eicosatetraenic acid (12-HETE) as their main metabolite. The placental release of 12-HETE was significantly decreased in hypertensive pregnancies. In hypertensive pregnancies the ratio TXB2/6-keto-PGF1 alpha synthesis was increased. Lipoxygenase metabolites, especially 12-HETE, seem to have important physiological and pathophysiological functions in the intrauterine compartment. Their biological role in this context needs further investigation.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Chromatography, High Pressure Liquid; Eicosanoids; Female; HELLP Syndrome; Humans; Hydroxyeicosatetraenoic Acids; Hypertension; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Uterus

The formation of lipoxygenase metabolites by human uterine and intrauterine tissues was evaluated using [1-14C]arachidonic acid (AA) as substrate. The major lipoxygenase product synthesized by human amnion, decidua vera and placenta was identified as 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE); smaller amounts of 5-HETE and 5-HETE (lactone form) were also formed. In chorion laeve only a trace amount of 12-HETE was detected. Human myometrium and cervical tissue converted [1-14C]AA to 5-HETE and 12-HETE in almost equal amounts. The formation of lipoxygenase products in all tissues was markedly inhibited by nordihydroguaiaretic acid (NDGA) an inhibitor of lipoxygenase activity and slightly stimulated or inhibited by indomethacin, an inhibitor of cyclooxygenase activity. These results are indicative that uterine and intrauterine tissues are probably potential sources of lipoxygenase products during pregnancy and parturition. Since 12-hydroperoxy-eicosatetraenoic acid (12-HPETE), the labile precursor of 12-HETE potently inhibits prostacyclin biosynthesis, our findings are suggestive of the possibility that aberrant lipoxygenase activities may contribute to the complications of pre-eclampsia.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 5,8,11,14-Eicosatetraynoic Acid; Arachidonic Acid; Arachidonic Acids; Catechols; Cervix Uteri; Epoprostenol; Female; Humans; Hydroxyeicosatetraenoic Acids; Indomethacin; Lipoxygenase; Masoprocol; Myometrium; Pre-Eclampsia; Pregnancy; Prostaglandins; Uterus