β-Carotene Attenuates Peroxide-Induced Vasoconstriction in the Human Placenta

Abstract

Objective: Placental lipid peroxides and thromboxane are abnormally increased in preeclampsia. Peroxides stimulate thromboxane to increase placental vasoconstriction. antioxidants, such as β-carotene, control lipid peroxidation. Reduced levels of βcarotene (0.25 μmol/L) have been found in preeclamptic women. We hypothesized that normal (0.5 μmol/L) or elevated (1.0 μmol/L) levels of β-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 μmol/L t-butyl hydroperoxide, and then with progressively increasing concentrations of β-carotene (0.25, 0.5, and 1 μmol/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 B₂ (TXB₂) and 6-keto-prostaglandin (PG)F_1α .

Results: Compared with control, t-butyl hydroperoxide significantly increased perfusion pressur, vascular resistance, and the secretion rates of lipid peroxides, TXB₂ and 6-keto-PGF_1α. Perfusion with normal (0.5 μmol/L) or increased (1 μmol/L) levels of β-carotene significantly or completely inhibited t-butyl hydroperoxide-induced vasoconstriction and the increases in lipid peroxide and TXB₂ secretion, but did not inhibit peroxide-induced increases in 6-keto-PGF_1α secretion. reduced levels of β-carotene (0.25 μmol/L) did not inhibit t-butyl hydroperoxide-induced vasoconstriction or the increases in lipid peroxide secretion.

Concluisons: β-carotene at levels found in normal pregnant women (0.5 μmol/L) or at levels achieved with β-carotene supplementation (1 μmol/L) inhibited peroxide-induced vasoconstriction and lipid peroxide and thromboxane secretion. Levels of β-carotene found in preeclamptic women (0.25 μmol/L) did not inhibit peroxide-induced vasoconstriction or lipid peroxide secretion.