Ma J J, Hou D Q, Zhang Q B, Korsten M A
Department of Pharmacology, Beijing Medical University, Beijing, P.R. China.
Digestion. 2001;63(2):102-7. doi: 10.1159/000051877.
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 In another study, rats drank nicotine solution for 20 days, after which the nicotine was withdrawn and replaced by water for 10 additional days.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 The gastric effects of nicotine persisted for at least 10 days after nicotine was withdrawn but then these effects could be abolished by prolonged NO treatment.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.
尼古丁通过减少胃黏膜血流量（GMBF）和黏液来加重实验性胃溃疡。由于一氧化氮（NO）可以改善这两个参数，我们评估了NO供体对给予尼古丁的大鼠乙醇诱导的胃黏膜损伤的影响。将尼古丁溶液或水给予Sprague-Dawley大鼠20天。在制备离体胃腔并暴露于乙醇前60分钟和10分钟给予NO供体（硝酸异山梨酯）。长期摄入尼古丁显著降低了GMBF和胃黏液含量。尼古丁加剧了乙醇诱导的胃损伤，短期给予NO供体未能拮抗尼古丁或酒精的致溃疡作用。在另一项研究中，大鼠饮用尼古丁溶液20天，之后停用尼古丁并换为水再持续10天。在这最后的10天期间给予NO供体。尼古丁停用后，其对胃的影响持续至少10天，但随后这些影响可通过延长NO治疗而消除。尼古丁降低血浆亚硝酸盐水平，但胃黏膜MPO活性保持不变。我们的数据表明，戒烟并延长NO供体给药时间可以完全消除尼古丁对胃的影响。
