Physiological and pathophysiological roles of nitric oxide in the central nervous system.

Nitric oxide (NO) is produced by three distinct isoforms of nitric oxide synthases in the central nervous system. Here, the roles of nitric oxide in the central nervous system are reviewed under physiological and pathophysiological conditions. Under physiological conditions, NO plays a role in the regulation of cerebral blood flow and autoregulation, blood flow-metabolism coupling, neurotransmission, memory formation, modulation of neuroendocrine functions, and behavioral activity. Impairment of the NO-mediated cerebrovascular vasodilatation occurs during ischemia-reperfusion, diabetes, hypertension, subararchnoid hemorrhage, and various forms of shock. Enhancement of NO production in the brain occurs during stoke, seizures, and acute and chronic inflammatory and neurodegenerative disorders. The alterations of the expression of the various isoforms of nitric oxide synthases under the above conditions are discussed. Moreover, the molecular mechanisms of NO and peroxynitrite induced cellular injury are delineated. Finally, the current strategies available for selective pharmacological manipulation of individual nitric oxide synthase isoforms are discussed.