NITRIC-OXIDE IN PHYSIOLOGY AND PATHOLOGY

Nitric oxide (NO) can exert a multitude of biological actions. NO, formed from L-arginine by a calcium-dependent enzyme (NO synthase) plays a key physiological role in regulating vascular tone and integrity. NO, formed by a constitutive neuronal isoform of NO synthase, likewise plays an important neuromodulator role. By contrast, high levels of NO can be generated following induction of a calcium-independent isoform of NO synthase. This excessive production of NO can provoke hypotension such as that observed in septic shock, and can exert cytotoxic actions leading to tissue injury and inflammation. Selective inhibitors of this inducible isoform thus have therapeutic potential in a number of disease states.