INCREASED NITROTYROSINE IN THE DIABETIC PLACENTA - EVIDENCE FOR OXIDATIVE STRESS

OBJECTIVE - To evaluate the presence of nitrotyrosine (NT) residues in placental villous tissue of diabetic pregnancies as an index of vascu lar damage linked to oxidative stress. RESEARCH DESIGN AND METHODS - V illous tissue was collected and flash frozen after delivery from 10 cl ass C and D IDDM patients (37.9 +/- 3.2 weeks) and 10 normotensive pre gnant individuals (37.5 +/- 3.8 weeks). Serial sections of tissue were immunostained with specific antibodies to NT, endothelial nitric oxid e synthase (eNOS), inducible nitric oxide synthase (iNOS), and mangane se superoxide dismutase (MnSOD). Sections were scored for intensity of immunostaining (0-3) by three observers blinded to the identity of ti ssue. RESULTS - All tissues demonstrated immunostaining for eNOS in bo th syncytiotrophoblast and stem villous vascular endothelium with no a pparent differences between groups. Immunostaining for iNOS was seen i n the villous stroma, but again was not different between the two grou ps. Significantly more intense NT staining was apparent in vascular en dothelium and villous stroma (both P < 0.02) of diabetic placentas. Th e endothelium of large villous vessels of diabetic tissues also showed more intense immunostaining for MnSOD (P < 0.01). CONCLUSIONS - In th ese diabetic pregnancies, we were unable to show increased eNOS, unlik e previous findings in preeclamptic pregnancies. The presence of NT ma y indicate vascular damage in the diabetic placenta due to peroxynitri te action formed from increased synthesis/interaction of nitric oxide and superoxide. The apparently paradoxical increase in MnSOD expressio n may be an adaptive response to increased superoxide generation.