GESTATIONAL DIABETES ALTERS HUMAN PLACENTAL VASCULAR-RESPONSES TO CHANGES IN OXYGEN-TENSION

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: Isola ted placental arteries and veins from women with well-controlled gesta tional diabetic and uncomplicated term pregnancies were precontracted with U46619 under 5% oxygen/5% carbon dioxide/balance nitrogen (P(O2) 35 to 38 torr) and then exposed to hypoxia (95% nitrogen/5% carbon dio xide) atmosphere (P(O2) 8 to 10 torr) for 5 to 7 minutes followed by r apid reoxygenation. Cumulative doses of hydrogen peroxide (1 to 100 mu mol/L) were added at 2-minute intervals. The studies were conducted in both the presence and the absence of endothelium. Prostaglandin invol vement was examined by treatment with indomethacin. Analysis of varian ce 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 norma l vessels. Placental vessels of women with gestational diabetes were f ound to undergo a significantly larger contraction than normal vessels when exposed to posthypoxic reoxygenation or micromolar concentration s of hydrogen peroxide. Both responses were eliminated and reversed to a relaxation by pretreatment with 10 mumol/L indomethacin in both ges tational diabetic and normal vessels, consistent with mediation throug h the formation of prostaglandins. Removal of the endothelium did not appear to alter any of the observed responses. CONCLUSIONS: Gestationa l diabetes produces an enhancement of the observed relaxation caused b y hypoxia and the contraction produced by reoxygenation or hydrogen pe roxide.