A NITRIC OXIDE-RELEASING NONSTEROIDAL ANTIINFLAMMATORY DRUG ACCELERATES GASTRIC-ULCER HEALING IN RATS

Background and Aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) hav e well-characterized inhibitory effects on gastric ulcer healing. A ne w class of gastrointestinal-sparing, nitric oxide-releasing NSAID deri vatives has been recently described. This study was performed to deter mine if one of these compounds (nitrofenac) would influence healing of a preexisting ulcer. Methods: Seven days after Induction of gastric u lcer with serosal acetic acid, daily oral treatment with antiinflammat ory doses of diclofenac, nitrofenac, or vehicle was started. After 7 d ays of treatment, the ulcer area was measured. The effects of misopros tol and two drugs that show in vitro selectivity for inhibiting cycloo xygenase 2 (nabumetone and L745,337) were also assessed. Results: Dicl ofenac, nabumetone, and L745,337 had no effect on ulcer healing when c ompared with vehicle. Only diclofenac significantly decreased hematocr it and weight gain. On the other hand, nitrofenac significantly accele rated healing. Glyceryl trinitrate also significantly and dose depende ntly accelerated healing. Nitrofenac suppressed cyclooxygenase 1 activ ity to a similar extent as dictofenac. Conclusions: These results show that an NO-releasing NSAID derivative and an NO donor could accelerat e ulcer healing, whereas a standard NSAID, misoprostol, and two inhibi tors of cyclooxygenase 2 had no effect. In addition to sparing the gas trointestinal tract, NO-releasing NSAIDs, despite suppressing cyclooxy genase activity, are capable of accelerating tissue repair.