Peculiarities of Effects of Nonsteroidal Anti-inflammatory Drugs on NO-synthase System in Gastric Mucosa of Rats under Stress Conditions

摘要

In experiments on rats with immobilization stress combined with water immersion, effects of nonsteroidal anti-inflammatory drugs (NSAIDs) of different genesis on the morphological status of gastric mucosa and changes in NO-synthase system activity were studied. An administration of naproxen, noncelective cyclooxygenase inhibitor, to rats with water-restrained stress enhanced strucrural hemorrhagic gastric mucosal lesions. At that, the activities of both isoforms of NO-sythase (inducible and constitutive) decreased, but lipoperoxidation processes remained at the level of stress. The advantage of using H2S-releasing nonsteroidal anti-inflammatory drug ATB-346 is a cytoprotective effect of the latter manifested as a decrease in total area of gastric injury. However, lipoperoxidation processes and NO-syntase activity did not differ substantially from those in the group treated with napoxen, indicating the prevalence of parent molecule (naproxen) in the regulation of NO-system functioning. An administration of a compound 2A5DHT, a dual COX/LOX inhibitor, caused the decrease in gastric injury as compared to naproxen influence. An activity of iNOS remained much higher than under condition of naproxen action.