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

Abstract

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 F2α([Formula: see text] 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.