Alterations in relaxation to lactate and H2O2 in human placental vessels from gestational diabetic pregnancies

We determined whether alterations in the mechanism of relaxation to H2O2 po tentially contribute to the enhanced prostaglandin-mediated contractile res ponse to H2O2 and posthypoxic reoxygenation seen in human placental vessels of pregnancies with gestational diabetes mellitus (GDM). Isolated placenta l arteries and veins from GDM and uncomplicated full-term pregnancies were precontracted with prostaglandin F-2 alpha (PO2 35-38 Torr) and then expose d to lactate (1-10 mM), arachidonic acid (0.01-10 mu M), nitroglycerin (1 n M-1 mu M), forskolin (0.01-10 mu M), or H2O2 (1 mu M-1 mM + 10 mu M indomet hacin). The rates of tissue H2O2 metabolism by catalase and nitrite product ion were measured. The relaxation to lactate was reduced in GDM placental a rteries and veins by 54-85 and 66-80%, and the relaxation to H2O2 was inhib ited by 80-94% in GDM placental veins compared with vessels from uncomplica ted full-term pregnancies. H2O2 caused only minimal relaxation of placental arteries. Responses to other relaxing agents were not altered in the GDM p lacental vessels. Diabetic vessels showed rates of nitrite production that were increased by 113-195% and rates of H2O2 metabolism by catalase that we re decreased by 44-61%. The loss of relaxation to H2O2 and lactate (mediate d via H2O2), perhaps as a result of the inhibition of catalase by nitric ox ide, may explain the previously reported enhancement of prostaglandin-media ted contractile responses to H2O2 and posthypoxic reoxygenation seen in GDM placental vessels.