NITROTYROSINE RESIDUES IN PLACENTA - EVIDENCE OF PEROXYNITRITE FORMATION AND ACTION

The interaction of nitric oxide and superoxide produces peroxynitrite anion, a strong, lane-lived oxidant with pronounced deleterious effect s that may cause vascular damage. The formation and action of peroxyni trite can br detected by immunohistochemical localization of nitrotyro sine residues, We compared the presence and localization of nitrotyros ine and of the endothelial isoform of nitric oxide synthase in placent al villous tissue from normotensive pregnancies (n = 5) with pregnanci es complicated by preeclampsia (n = 5). intrauterine growth restrictio n (n = 5), and preeclampsia plus intrauterine growth restriction (n = 4), conditions characterized by increases in fetoplacental vascular re sistance, fetal platelet consumption: and fetal morbidity and mortalit y. In all tissues, absent or faint nitrotyrosine immunostaining but pr ominent nitric oxide synthase immunostaining were found in syncytiotro phoblast. In tissues from normotensive pregnancies, faint nitrotyrosin e immunostaining was found in vascular endothelium. and nitric oxide s ynthase was present in stem villous endothelium but not in the termina l villous capillary endothelium. In contrast, in preeclampsia and/or i ntrauterine growth restriction, moderate to intense nitrotyrosine immu nostaining was seen in villous vascular endothelium, and immunostainin g was also seen in surrounding vascular smooth muscle and villous stro ma. The intensity of nitrotyrosine immunostaining in preeclampsia (wit h or without intrauterine growth restriction) was significantly greate r than that of controls. Intense nitric oxide synthase staining was se en in endothelium of stem villous vessels and the small muscular arter ies of the terminal villous region in these tissues and may be in adap tive response to the increased resistance, The presence of nitrotyrosi ne residues, particularly in the endothelium, may indicate the formati on and action of peroxynitrite, resulting in vascular damage that cont ributes to the increased placental vascular resistance.