Nitric oxide releasing drugs: from bench to bedside.

NO biology has had an enormous boost and several aspects of its role in physiology and pathology has been extensively studied. NO acts as a double edge sword mediator that has beneficial physiological effects as well as detrimental pathological effects making very difficult to develop drugs. Studies on nitric oxide therapeutic approach can be divided into two simple approaches: one directed to increase the NO release and another to inhibit NO release. Gene therapy approach have been also developed and pre-clinical data on iNOS and eNOS have shown promising results in post-angioplasty restenosis. The major limitation to the use of NSAID is represented by their ability to cause ulceration and bleeding in the gastrointestinal tract NO plays an important role in GI integrity. NO releasing NSAID have higher GI tolerability and retain their anti-inflammatory activity as well as the ability to inhibit platelet aggregation. NO-NSAIDs not only represents a new class of drugs but they represent the first "proof of concept" on the key role of NO in the gastrointestinal homeostasis.