iNOS Via Peroxynitrite Overformation Mediates Aortic Endothelial Injury in Diabetic Rats

Objective Oxidative stress is an important mechanism in the development of chronic complications in diabetes mellitus, and endothelial injury plays a key role in the pathogenesis of diabetic vascular injury. The present study was to investigate the role of inducible nitric oxide synthase (iNOS) induced peroxynitrite (ONOO-) in the aortic endothelial injury of diabetic rats.Methods/Results: Using RT-PCR, the mRNA of iNOS and nitrotyrosine (NT), a specific marker of ONOO-, were showed a significantly increased in the aortic endothelial diabetic rats, which was induced by streptozocin (STZ) and its increased protein content and distribution level were identified by Western blot and immunohistochemistry, respectively. Light microscope (hematocylin-eosin staining) and electron microscope (scanning and transmission) were employed to observe the morphological damage including nuclear shedding, mitochondria injury and inflammatory cell infiltration. We also measured the biochemical indicators of the diabetic rats, and the content of malondialdehyde (MDA), nitric oxide (NO), iNOS, endothelin (ET), and thromboxane B2 (TXB2) were increased and superoxide dismutase (SOD) was decreased. Conclusion: This study clarified that iNOS and its resultant exaggerated ONOO- formation, and this may play a key role in aortic endothelial injury of the diabetic rats. Thus, anti-iNOS maybe a potential therapy to prevent the ONOO- mediated oxidative stress injury.