Under glucose-deprived conditions, astrocytes rapidly underwent death due to their increased susceptibility to endogenously produced peroxynitrite (Gila 31, 155-164; J. Neuroimmunol. 112, 55-62; J. Neurochem. 74, 1989-1998). In the present study, the cell membrane-permeable synthetic superoxide dismutase (SOD) mimetic cyclam manganese(III) 1,4,8,11-tetraazacyclodecane (Mn(III)-cyclam) completel...

Repeated use of opiate analgesic drugs such as morphine for the relief of chronic pain may result in the development of opiate tolerance and dependence, leading to a narrowing of the drug's therapeutic index and increased side effects. Previous preclinical work has shown that interruption of a signaling cascade involving the N-methyl-D-aspartate receptor and NO prevents morphine tolerance. In t...

Vascular aging is mainly characterized by endothelial dysfunction. We found decreased free nitric oxide (NO) levels in aged rat aortas, in conjunction with a sevenfold higher expression and activity of endothelial NO synthase (eNOS). This is shown to be a consequence of age-associated enhanced superoxide (.O(2)(-)) production with concomitant quenching of NO by the formation of peroxynitrite le...

Reactive nitrogen species are now considered to play an important role in various pathologies. Although the pathological significance of these molecules, peroxynitrite in particular, has long been attributed to their abilities to react with any component of the cells, including lipids, proteins, and DNA, a paradigm shift has recently been occurring whereby reactive nitrogen species are apprecia...