beta-carotene attenuates peroxide-induced vasoconstriction in the human placenta

OBJECTIVE: Placental lipid peroxides and thromboxane are abnormally increased in preeclampsia. Peroxides stimulate thromboxane to increase placental vasoconstriction. Antioxidants, such as beta-carotene, control lipid peroxidation. Reduced levels of beta-carotene (0.25 mu mol/L) have been found in preeclamptic women. We hypothesized that normal (0.5 mu mol/L) or elevated (1.0 mu mol/L) levels of beta-carotene would attenuate peroxide-induced vasoconstriction in the human placenta, whereas low levels would not. METHODS: Isolated human placental cotyledons (n = 8) were sequentially perfused with control Krebs-Ringer-bicarbonate buffer, 200 mu mol/L t-butyl hydroperoxide, and then with progressively increasing concentrations of beta-carotene (0.25, 0.5, and 1 mu mol/L) plus t-butyl hydroperoxide. Fetal perfusion pressure was monitored continuously, and maternal and fetal effluent samples were collected for each treatment. Samples were analyzed for lipid peroxides and for thromboxane and prostacyclin by their stable metabolites thromboxane B-2 (TXB(2)) and 6-keto-prostaglandin (PG)F-1 alpha. RESULTS: Compared with control, t-butyl hydroperoxide significantly increased perfusion pressure, vascular resistance, and the secretion rates of lipid peroxides, TXB(2) and 6-keto-PGF(1 alpha). Perfusion with normal (0.5 mu mol/L) or increased (1 mu mol/L) levels of beta-carotene significantly or completely inhibited t-butyl hydroperoxide-induced vasoconstriction and the increases in lipid peroxide and TXB(2) secretion, but did not inhibit peroxide-induced increases in 6-keto-PGF(1 alpha) secretion. Reduced levels of beta-carotene (0.25 mu mol/L) did not inhibit t-butyl hydroperoxide-induced vasoconstruction or the increases in lipid peroxide secretion. CONCLUSIONS: beta-carotene at levels found in normal pregnant women (0.5 mu mol/L) or at levels achieved with beta-carotene supplementation (1 mu mol/L) inhibited peroxide-induced vasoconstriction and lipid peroxide and thromboxane secretion. Levels of beta-carotene found in preeclamptic women (0.25 mu mol/L) did not inhibit peroxide-induced vasoconstriction or lipid peroxide secretion. Copyright (C) 1997 by the Society for Gynecologic Investigation.