TOPICAL NICOTINE PROTECTS RAT GASTRIC-MUCOSA AGAINST ASA-INDUCED DAMAGE - A ROLE FOR MUCOSAL FLUID SECRETION IN CYTOPROTECTION

Acute intragastric nicotine administration has previously been shown t o protect against ethanol-induced gastric mucosal damage. The aim of t his study was to examine the effects of acute nicotine exposure on ASA -induced gastric mucosal damage and to determine if nicotine's protect ive effect is secondary to an increase in mucosal blood flow or in muc osal fluid secretion, as reflected by changes in the juxtamucosal pH g radient and volume of intragastric fluid. Mucosal blood flow, using a laser Doppler flowmeter, juxtamucosal pH gradient (depth, magnitude, a nd surface pH), using antimony microelectrodes, and changes in volume of luminal bathing solutions were measured in rat ex vivo gastric cham ber preparations prior to and after a 10-min exposure to topical nicot ine (1 mg in 8 ml of 0.2 M mannitol in 50 mM HCl), or to mannitol-HCl solution (vehicle). This was followed by application of acidified ASA (80 mM in 160 mM HCl) to the chambered mucosae for 10 min. Lesion area , expressed as the percentage of total glandular mucosa which was dama ged, was significantly (P < 0.05) reduced by nicotine pretreatment. Bl ood flow decreased with nicotine exposure by 18.4%, compared to 13.6% in the control group (NS). Both gradient depth and gastric fluid volum e increased significantly in the nicotine group (P < 0.05) compared to controls. Yohimbine pretreatment prevented both the increase in juxta mucosal pH gradient depth and the protective effect of nicotine. These results suggest that acute intragastric nicotine exposure protects ag ainst ASA-induced gastric damage in rats. This protection is not due t o increased mucosal blood flow, but may be due to increased mucosal se cretion, as reflected by an increase in the pH gradient depth, and an increase in the intragastric volume.