OBJECTIVE: Our objective was to study tone responses caused by hypoxia, reoxygenation, and hydrogen peroxide in human placental vessels from gestational diabetic and normal term pregnancies. STUDY DESIGN: Isolated placental arteries and veins from women with well-controlled gestational diabetic and uncomplicated term pregnancies were precontracted with U46619 under 5% oxygen/5% carbon dioxide/balance nitrogen (PO2 35 to 38 torr) and then exposed to hypoxia (95% nitrogen/5% carbon dioxide) atmosphere (PO2 8 to 10 torr) for 5 to 7 minutes followed by rapid reoxygenation. Cumulative doses of hydrogen peroxide (1 to 100 μmol/L) were added at 2-minute intervals. The studies were conducted in both the presence and the absence of endothelium. Prostaglandin involvement was examined by treatment with indomethacin. Analysis of variance and t test statistics were used. RESULTS: After incubation under 5% oxygen, hypoxia caused a larger prostaglandin-independent relaxation in arteries and veins of women with gestational diabetes than in normal vessels. Placental vessels of women with gestational diabetes were found to undergo a significantly larger contraction than normal vessels when exposed to posthypoxic reoxygenation or micromolar concentrations of hydrogen peroxide. Both responses were eliminated and reversed to a relaxation by pretreatment with 10 μmol/L indomethacin in both gestational diabetic and normal vessels, consistent with mediation through the formation of prostaglandins. Removal of the endothelium did not appear to alter any of the observed responses. CONCLUSIONS: Gestational diabetes produces an enhancement of the observed relaxation caused by hypoxia and the contraction produced by reoxygenation or hydrogen peroxide.