Reversal of the gastric effects of nicotine by nitric oxide donor treatment

Nicotine intensifies experimental gastric ulceration by reducing gastric mu cosal blood flow (GMBF) and mucus. As both these parameters can be improved by nitric oxide (NO), we evaluated the impact of a NO donor in ethanol-ind uced gastric mucosal injury in rats administered nicotine. A nicotine solut ion or water was administered for 20 days to Sprague-Dawley rats. NO donor (isosorbide dinitrate) was given 60 and 10 min before preparation of ex viv o gastric chambers and exposure to ethanol. Chronic nicotine intake signifi cantly reduced GMBF and gastric mucus content. Nicotine intensifies ethanol -induced gastric injury and short-term administration of NO donor failed to antagonize the ulcerogenic action from either nicotine or alcohol. In anot her study, rats drank nicotine solution for 20 days, after which the nicoti ne was withdrawn and replaced by water for 10 additional days. NO donor was provided during these last 10 days. The gastric effects of nicotine persis ted for at least 10 days after nicotine was withdrawn but then these effect s could be abolished by prolonged NO treatment. Nicotine reduces plasma nit rite level, but gastric mucosal MPO activity remained unchanged. Our data s uggest that nicotine cessation plus a longer period of NO donor administrat ion can completely abolish the gastric effects of nicotine. Copyright (C) 2 001 S. Karger AG, Basel.