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Long-term diabetes mellitus is characterized by impaired endothelium-dependent relaxation. In contrast, there is limited information on endothelial function in the early stages of the disease. In this study, we evaluated endothelial function ex vivo at early, intermediate and later stages of streptozotocin (STZ)-induced diabetes mellitus. We also evaluated(More)
  • G M Pieper
  • 1997
Tetrahydrobiopterin is a cofactor for nitric oxide synthase. In low concentrations of this cofactor, nitric oxide synthase is known to produce less nitric oxide and, correspondingly, enhanced quantities of the oxidant species, hydrogen peroxide. In this study, we tested the hypothesis that an exogenous tetrahydrobiopterin derivative might improve(More)
OBJECTIVE Previous studies suggest a role of superoxide anion radicals (.O2-) in impaired endothelium-dependent relaxation of diabetic blood vessels; however, the role of secondary reactive oxygen species remains unclear. In the present study, we investigated a role of various potential reactive oxygen species in diabetic endothelial dysfunction. METHODS(More)
Diabetic complications are believed to arise, in part, through an increase in oxidative stress. We characterized antioxidant status in vascular tissue in untreated diabetic rats and in diabetic rats rendered euglycemic by pancreatic islet transplantation. Three key endogenous antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione(More)
Acute histologic and ultrastructural changes, quantification and regional distribution (transmural, circumferential, transaxial) of damaged myocells from anesthetized, open-chested dogs following one hour of intravenous infusions of saline or increasing doses of isoproterenol (0.1, 1.0, 2.5 micrograms/kg/min) or norepinephrine (4.0 micrograms/kg/min) were(More)
BACKGROUND Nitration of a critical tyrosine residue in the active site of manganese superoxide dismutase (MnSOD) can lead to enzyme inactivation. In this study, we examined the effect of inducible nitric oxide synthase (iNOS) on MnSOD expression, activity and nitration in acutely rejecting cardiac transplants. METHODS Lewis (isograft) or Wistar-Furth(More)
The present experiments were conducted to determine whether endothelium-dependent relaxation is impaired in chronic (10-12 wk), streptozotocin-induced diabetic rat aortas and to determine the specificity and sensitivity of diabetic vasculature to oxygen-derived free radicals. Endothelium-dependent relaxation by acetylcholine and ADP was severely impaired in(More)
Brief (15-minute) coronary occlusion and subsequent reperfusion lead to prolonged functional and metabolic abnormalities (stunned myocardium). Previous work suggests that one factor responsible for this phenomenon is oxygen-derived free radicals. The formation of the highly reactive hydroxyl radical requires the presence of metal ions, most importantly(More)
Electron spin resonance (ESR) spectroscopy together with spin trapping techniques and the application of state-of-the-art loop gap resonators was used to provide a direct measure of spontaneous oxygen radical production by homogenates of freshly isolated and cultured rat pancreatic islets. Using the spin trap agent, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO),(More)