ROLE OF VASOACTIVE-INTESTINAL-PEPTIDE (VIP) IN PATHOGENESIS OF ETHANOL-INDUCED GASTRIC-MUCOSAL DAMAGE IN RATS

To elucidate the possible role of vasoactive intestinal peptide (VIP) in the pathogenesis of acute gastric mucosal damage, rats were treated intragastrically with 1.0 ml 96% ethanol with or without intravenous or intraperitoneal coadministration of VIP (1 nmol/liter to 1 mumol/li ter/100 g). VIP was found to double the mean lesion area when compared with that induced by ethanol alone (P < 0.05), an effect that was pre vented by VIP antagonist (1 mumol/liter/100 g). A substance P antagoni st (1 mumol/liter/100 g) also reduced the extent of gastric damage ind uced by coadministration of VIP and ethanol. VIP antagonist or substan ce P antagonist significantly reduced ethanol-induced gastric mucosal damage. Gastric mucosal levels of LTB4, LTC4, VIP, and substance P wer e significantly increased in ethanol-treated rats as compared with sal ine-treated animals (P < 0.05). The augmentation of ethanol-induced da mage by VIP was associated with increased gastric mucosal levels of LT B4. In VIP-treated rats, gastric mucosal levels of substance P were fo und to be significantly increased compared with control rats (P < 0. 0 5). Administration of VIP to pyloric-ligated rats significantly increa sed gastric acid output and blood pepsinogen A levels as compared with saline treated rats (P < 0. 05). Ketotifen, a mast cell stabilizer (1 00 mug/100 g), administered orally 30 min before damage induction by e thanol, with or without VIP, totally abolished the damage of the surfa ce epithelium of the entire gastric mucosa and significantly reduced t he mucosal levels of LTC4 and LTB4 (P < 0.05). It is suggested that VI P is involved in the pathogenesis of acute ethanol-induced gastric muc osal damage. The effective mucosal protection by ketotifen suggests a role for mast cells and their mediators in the pathogenesis of acute g astric mucosal damage.