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 to protect against ethanol-induced gastric mucosal damage. The aim of this study was to examine the effects of acute nicotine exposure on ASA-induced gastric mucosal damage and to determine if nicotine's protective effect is secondary to an increase in mucosal blood flow or in mucosal fluid secretion, as reflected by changes in the juxtamucosal pH gradient and volume of intragastric fluid. Mucosal blood flow, using a laser Doppler flowmeter, juxtamucosal pH gradient (depth, magnitude, and surface pH), using antimony microelectrodes, and changes in volume of luminal bathing solutions were measured in rat ex vivo gastric chamber preparations prior to and after a 10-min exposure to topical nicotine (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 damaged, was significantly (P < 0.05) reduced by nicotine pretreatment. Blood flow decreased with nicotine exposure by 18.4%, compared to 13.6% in the control group (NS). Both gradient depth and gastric fluid volume increased significantly in the nicotine group (P < 0.05) compared to controls. Yohimbine pretreatment prevented both the increase in juxtamucosal pH gradient depth and the protective effect of nicotine. These results suggest that acute intragastric nicotine exposure protects against ASA-induced gastric damage in rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Fallone
C A
CA
Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada.
Morris
G P
GP
D000287:Administration, Topical; D000818:Animals; D001241:Aspirin / Q000633:toxicity*; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D017078:Laser-Doppler Flowmetry; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D015016:Yohimbine / Q000494:pharmacology
D015016:Yohimbine; D009538:Nicotine; D001241:Aspirin