Biology of nitric oxide signaling

The free radical nitric oxide (NO) has emerged in recent years as a fundame ntal signaling molecule for the maintenance of homeostasis, as well as a po tent cytotoxic effector involved in the pathogenesis of a wide range of hum an diseases. Although this paradoxical fate has generated confusion, separa ting the biological actions of NO on the basis of its physiologic chemistry provides a conceptual framework which helps to distinguish between the ben eficial and toxic consequences of NO, and to envision potential therapeutic strategies for the future. Under normal conditions, NO produced in low con centration acts as a messenger and cytoprotective (antioxidant) factor, via direct interactions with transition metals and other free radicals. Altern atively, when the circumstances allow the (formation of substantial amounts of NO and modify the cellular microenvironment formation of the superoxide radical), the chemistry of NO will turn into indirect effects consecutive to the formation of dinitrogen trioxide and peroxynitrite. These "reactive nitrogen species" will, in turn, mediate both oxidative and nitrosative str esses, which form the basis of the cytotoxicity generally attributed to NO, relevant to the pathophysiology of inflammation, circulatory shock, and is chemia-reperfusion injury.