[23] Oxidative chemistry of peroxynitrite

Publisher Summary Nitric oxide (.NO) is an important and largely unrecognized mediator of oxygen radical injury because it contains an unpaired electron that readily combines with many free radicals. Endothelium and neurons produce nitric oxide as an intercellular messenger, which has important roles in vasoregulation and synaptic plasticity. Nitric oxide reacts rapidly with superoxide to form the strong oxidant, peroxynitrite anion (ONOO - ). Activated macrophages and neutrophils can produce nitric oxide and superoxide at similar rates. This chapter presents that essentially all of the nitric oxide produced by rat alveolar macrophages activated with phorbol ester is converted to peroxynitrite. Peroxynitrite is not a free radical because the unpaired electrons on nitric oxide and superoxide have combined to form a new N–O bond in peroxynitrite. Peroxynitrite anion can be stored for weeks in alkaline solution or even entrapped in solid forms. During its decomposition at physiological pH, peroxynitrite can produce some of the strongest oxidants known in a biological system, initiating reactions characteristic of hydroxyl radical, nitronium ion, and nitrogen dioxide. The unusual stability of peroxynitrite as an anion contributes to its toxicity by allowing it to diffuse far from its site of formation while being selectively reactive with cellular targets.