Effect of cigarette smoke on ethanol-induced gastric mucosal lesions: The role of nitric oxide and neutrophils

The roles of neutrophil aggregation, inducible nitric oxide synthase activation and chemoattractant, leukotriene B(4), in potentiation of the cigarette smoke effect on ethanol-induced gastric mucosal damage were studied. Smoke exposure markedly increased gastric lesion formation following ethanol administration and this was accompanied by substantial increase in gastric mucosal leukotriene B(4) concentration, myeloperoxidase and inducible nitric oxide synthase activities. Antineutrophil serum or aminoguanidine pretreatment significantly attenuated both gastric mucosal lesion formation and inducible nitric oxide synthase activity. The increased myeloperoxidase activity was abolished by antineutrophil serum but not by aminoguanidine. These data indicated that both neutrophil mobilization and inducible nitric oxide synthase activation in the gastric mucosa play an important role in the potentiating action of cigarette smoke on ethanol-induced gastric mucosal lesion formation. Increased synthesis of nitric oxide fr om inducible nitric oxide synthase during gastric damage may be secondary to neutrophil infiltration in the gastric mucosa. Chemoattractant leukotriene B(4) could also contribute to neutrophil recruitment in the tissue. (C) 1998 Elsevier Science B.V.