Cytoprotective vs. Cytotoxic effects of nitric oxide in ischemic and inflammatory bowel disease

Nitric oxide is a simple molecule that exerts complex physiologic and pathophysiologic effects in mammalian biologic systems. The biosynthesis of NO is controlled by the availability of the substrate and enzyme, L-arginine and NOS, respectively. Nitric oxide derived from cNOS is principally involved in cytoprotective functions including vasodilatation, inhibition of platelet aggregation and adhesion, inhibition of neutrophil adhesion and emigration, and non vascular smooth muscle relaxation. On the other hand, iNOS-derived NO is involved with cytoxicity via the synthesis of peroxynitrite through the reaction of NO with superoxide. The cNOS-derived NO exerts a predominanty anti-inflammatory effect during acute gastrointestinal tract inflammation such as intestinal I-R injury, whereas iNOS-derived NO serves principally as a pro-inflammatory agent during chronic gastrointestinal tract inflamamtion such as IBD. Administration of NO donors during early stages and selective iNOS inhibitors during later stages of of gastrointestinal inflammation appear to have therapeutic potential.