ABSTRACT
Experimental evidence has shown that cigarette smoking potentiates ulcer formation and delays ulcer healing. The exact mechanisms are still not completely defined. We investigated the effects of cigarette smoking on P selectin expression and its actions on neutrophil infiltration and nitric oxide formation in ethanol-induced gastric mucosal damage. In the present study, rats were exposed to cigarette smoke for three 1 h periods. Cigarette smoke exposure significantly up-regulated P selectin expression in the gastric mucosa. Cigarette smoke exposure following ethanol challenge substantially potentiated the mucosal damage, which was accompanied with an increase in myeloperoxidase and inducible nitric oxide synthase activities. Anti-neutrophil serum completely abolished these changes, whereas aminoguanidine produced similar effects without affecting myeloperoxidase activity. Taken together, cigarette smoke exposure can up-regulate P selectin expression, which facilitates neutrophil rolling, margination and infiltration when challenged with ethanol. These actions activate inducible nitric oxide synthase activity, which may contribute to the potentiating effect of cigarette smoking on ethanol-induced gastric ulceration in rats.