MECHANISTIC STUDY OF ADVERSE ACTIONS OF CIGARETTE-SMOKE EXPOSURE ON ACETIC ACID-INDUCED GASTRIC-ULCERATION IN RATS

Cigarette smoking is associated with peptic ulceration in humans. A me chanistic study of the potentiating effects of cigarette smoking on ac etic acid-induced gastric ulceration in rats was hence performed. Rats were exposed to 0, 2 or 4% of cigarette smoke for three l-hr periods during the 24 hr starvation before ulcer induction. Cigarette smoke ex posure potentiated ulcer formation which was accompanied by a reductio n of gastric blood flow at the ulcer base and ulcer margin. Further st udies showed that cigarette smoke exposure alone did not cause any mac roscopic injury in the stomach but significantly decreased the basal g astric blood flow in a concentration-dependent manner, which was coupl ed with an increase in mucosal xanthine oxidase (XO) activity. Pretrea tment with allopurinol (Allo, 5 mg/kg, iv), a XO inhibitor, partially prevented the potentiating effect of cigarette smoke exposure on ulcer formation and also significantly improved the gastric blood flow. Ulc er induction itself dramatically increased constitutive nitric oxide s ynthase (cNOS) activity and prostaglandin E-2 (PGE(2)) level in the ga stric mucosa. However, the increment of cNOS activity but not PGE(2) l evel was markedly attenuated by cigarette smoke exposure. Sodium nitro prusside (SNP, 25 or 50 mu g/kg, iv), a nitric oxide (NO) donor, compl etely abolished the potentiating effect of cigarette smoke exposure on ulcer formation and also reversed the adverse effect on gastric blood flow. Thus, XO activation and cNOS reduction in the gastric mucosa ar e closely associated with the potentiating action of cigarette smoke e xposure on ulcer formation in rats.