Nitric oxide and the gut injury induced by non-steroidal anti-inflammatory drugs.

Nitric oxide (NO) can protect the gastrointestinal tract from injury, including that provoked by non-steroidal anti-inflammatory drugs (NSAIDs). This protective profile of NO, which predominantly reflects actions on the microcirculation, is mimicked by NO donors. Moreover, the NO-donating agents know as the NO-NSAIDs or CINODs (cyclo-oxygenase-inhibiting nitric oxide-donating drugs) exhibit reduced gut injury in experimental models, which is considered to reflect these local beneficial actions of NO. NSAIDs cause chronic inflammatory lesions in the small intestine in experimental models. This injury results from initial COX inhibition and other local events, with translocation of indigenous luminal bacteria, leading to induction of NO synthase isoform, iNOS, and subsequent production of the cytotoxic moiety, peroxynitrite from NO and superoxide. Agents that inhibit iNOS or superoxide production can attenuate such intestinal injury. In the absence of reactive oxygen moieties, NO may play a beneficial role in the resolution of inflammatory damage to the gut, thus reconciling the potential opposing properties of NO in tissue inflammation and injury.