15-hydroxy-5-8-11-13-eicosatetraenoic-acid and Pre-Eclampsia

A circulating factor derived from the placenta has been implicated in the pathogenesis of preeclampsia. The aim of this study was to determine whether placental extracts from normotensive women and women with preeclampsia increase oxidative metabolism and histamine-induced vasoconstriction in porcine carotid artery.. Placental extracts from normotensive women and women with preeclampsia were applied to porcine carotid artery, and oxidative metabolism was measured. Histamine-induced isometric force responses were also determined in the absence and presence of placental extracts.. Application of placental extracts to porcine carotid artery caused a fall in oxygen tension, which reflects increased consumption. Extracts from placentas taken from women with preeclampsia caused a greater fall than those from normotensive women (0.117 +/- 0.026 vs 0.018 +/- 0.0024 micromol oxygen per milligram; P < or =.01). Histamine-induced contractions were potentiated by extracts from preeclampsia but not from those of women without hypertension. The maximal steady-state force values were 13,137 +/- 3647, 12,921 +/- 3684, and 21,673 +/- 7189 N/m(-2) for control, normotensive, and preeclamptic samples at 10-micromol/L histamine (P < or =.05, compared with control placental extracts).. Placental extracts from women with preeclampsia cause a greater stimulation of porcine artery oxygen consumption and exacerbation of histamine-induced vasoconstriction than extracts from normotensive women.

Topics: Animals; Calcium; Carotid Arteries; Female; Histamine; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Isometric Contraction; Magnesium; Male; Oxidation-Reduction; Oxygen Consumption; Placenta; Pre-Eclampsia; Pregnancy; Swine; Tissue Extracts; Vasoconstriction

We tested the hypothesis that trophoblast produces 15-hydroxyeicosatetraenoic acid, and its level is elevated in trophoblast from preeclamptic women compared with normal. We also used selective enzymatic inhibitors to determine the relative contributions of 15-lipoxygenase and the two isozymes of prostaglandin H synthase to 15-hydroxyeicosatetraenoic acid levels.. Cytotrophoblasts isolated from placentas of normal or preeclamptic women were cultured in the presence or absence of enzyme inhibitors. Media levels of 15-hydroxyeicosatetraenoic acid were measured by radioimmunoassay.. When compared with normal pregnancies, cytotrophoblasts from preeclamptic pregnancies released up to fivefold higher levels of 15-hydroxyeicosatetraenoic acid. Aspirin, an inhibitor of both the prostaglandin H synthase-1 and prostaglandin H synthase-2 isozymes, and nordihydroguaiaretic acid, a selective inhibitor of lipoxygenases, both significantly inhibited 15-hydroxyeicosatetraenoic acid production. In contrast, the selective prostaglandin H synthase-2 inhibitor NS-398 had no effect on 15-hydroxyeicosatetraenoic acid release in the absence of aspirin, but NS-398 reduced 15-hydroxyeicosatetraenoic acid levels in normal trophoblast pretreated with aspirin.. The data indicate that 15-hydroxyeicosatetraenoic acid is produced in trophoblasts and its release by cytotrophoblasts is higher in preeclamptic pregnancies compared with normal controls. Both lipoxygenase and prostaglandin H synthase contribute to 15-hydroxyeicosatetraenoic acid production, and aspirin reduces 15-hydroxyeicosatetraenoic acid secretion. We suggest 15-hydroxyeicosatetraenoic acid plays a role in the oxidation of lipoproteins and the endothelial damage characteristic of preeclampsia.

Topics: Aspirin; Cells, Cultured; Cyclooxygenase Inhibitors; Female; Humans; Hydroxyeicosatetraenoic Acids; Isoenzymes; Lipoxygenase; Lipoxygenase Inhibitors; Masoprocol; Pre-Eclampsia; Pregnancy; Prostaglandin-Endoperoxide Synthases; Radioimmunoassay; Time Factors; Trophoblasts

Placentae from pregnancies complicated by pregnancy-induced hypertension (PIH) secrete significantly more 15-hydroxyeicosatetraenoic acid (15-HETE) than gestation-matched controls. 15-HETE and its hydroperoxy precursor can inhibit prostacyclin biosynthesis and may thus contribute to the pathological sequelae of PIH.

Topics: Epoprostenol; Female; Humans; Hydroxyeicosatetraenoic Acids; Placenta; Pre-Eclampsia; Pregnancy