Alterations in relaxation to lactate and H₂O₂in human placental vessels from gestational diabetic pregnancies

We determined whether alterations in the mechanism of relaxation to H₂O₂potentially contribute to the enhanced prostaglandin-mediated contractile response to H₂O₂and posthypoxic reoxygenation seen in human placental vessels of pregnancies with gestational diabetes mellitus (GDM). Isolated placental arteries and veins from GDM and uncomplicated full-term pregnancies were precontracted with prostaglandin F_2α($P{O}_2$ 35–38 Torr) and then exposed to lactate (1–10 mM), arachidonic acid (0.01–10 μM), nitroglycerin (1 nM–1 μM), forskolin (0.01–10 μM), or H₂O₂(1 μM–1 mM + 10 μM indomethacin). The rates of tissue H₂O₂metabolism by catalase and nitrite production were measured. The relaxation to lactate was reduced in GDM placental arteries and veins by 54–85 and 66–80%, and the relaxation to H₂O₂was inhibited by 80–94% in GDM placental veins compared with vessels from uncomplicated full-term pregnancies. H₂O₂caused only minimal relaxation of placental arteries. Responses to other relaxing agents were not altered in the GDM placental vessels. Diabetic vessels showed rates of nitrite production that were increased by 113–195% and rates of H₂O₂metabolism by catalase that were decreased by 44–61%. The loss of relaxation to H₂O₂and lactate (mediated via H₂O₂), perhaps as a result of the inhibition of catalase by nitric oxide, may explain the previously reported enhancement of prostaglandin-mediated contractile responses to H₂O₂and posthypoxic reoxygenation seen in GDM placental vessels.