Reversal of the gastric effects of nicotine by nitric oxide donor treatment.
Nicotine intensifies experimental gastric ulceration by reducing gastric mucosal 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-induced gastric mucosal injury in rats administered nicotine. A nicotine solution 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 vivo gastric chambers and exposure to ethanol. Chronic nicotine intake significantly 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 In another study, rats drank nicotine solution for 20 days, after which the nicotine was withdrawn and replaced by water for 10 additional days. NO donor was provided during these last 10 days. The gastric effects of nicotine persisted for at least 10 days after nicotine was withdrawn but then these effects could be abolished by prolonged NO treatment. Nicotine reduces plasma nitrite level, but gastric mucosal MPO activity remained unchanged. Our data suggest that nicotine cessation plus a longer period of NO donor administration can completely abolish the gastric effects of nicotine.
Ma
J J
JJ
Department of Pharmacology, Beijing Medical University, Beijing, P.R. China.
Hou
D Q
DQ
Zhang
Q B
QB
Korsten
M A
MA
D000704:Analysis of Variance; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity; D005752:Gastric Mucins / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D009573:Nitrites / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced
D005752:Gastric Mucins; D009573:Nitrites; D000431:Ethanol; D009538:Nicotine; D009195:Peroxidase; D007548:Isosorbide Dinitrate