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 mumol/L) have been found in preeclamptic women. We hypothesized that normal (0.5 mumol/L) or elevated (1.0 mumol/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 mumol/L t-butyl hydroperoxide, and then with progressively increasing concentrations of beta-carotene (0.25, 0.5, and 1 mumol/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)F1 alpha.


RESULTS
Compared with control, t-butyl hydroperoxide significantly increased perfusion pressure, vascular resistance, and the secretion rates of lipid peroxides, TXB2 and 6-keto-PGF1 alpha. Perfusion with normal (0.5 mumol/L) or increased (1 mumol/L) levels of beta-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-PGF1 alpha secretion. Reduced levels of beta-carotene (0.25 mumol/L) did not inhibit t-butyl hydroperoxide-induced vasoconstriction or the increases in lipid peroxide secretion.


CONCLUSIONS
beta-carotene at levels found in normal pregnant women (0.5 mumol/L) or at levels achieved with beta-carotene supplementation (1 mumol/L) inhibited peroxide-induced vasoconstriction and lipid peroxide and thromboxane secretion. Levels of beta-carotene found in preeclamptic women (0.25 mumol/L) did not inhibit peroxide-induced vasoconstriction or lipid peroxide secretion.
Cueto
S M
SM
Department of Obstetrics and Gynecology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0034, USA.
Romney
A D
AD
Wang
Y
Y
Walsh
S W
SW
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008054:Lipid Peroxides / Q000378:metabolism; D010477:Perfusion; D010545:Peroxides / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism; D011247:Pregnancy; D013929:Thromboxane B2 / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D019207:beta Carotene / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide
D000975:Antioxidants; D008054:Lipid Peroxides; D010545:Peroxides; D019207:beta Carotene; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D020122:tert-Butylhydroperoxide