Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis

Background: Ulcerative colitis is a condition of nonsmokers in which nicoti ne is of therapeutic benefit. Aims: To examine the in vitro effect of nicotine on colonic smooth muscle a ctivity and the role of nitric oxide (NO) as a mediator. Methods: Nicotine, 1-10 muM, was administered to strips of circular muscle from the distal sigmoid colon of 9 patients with active ulcerative colitis and 18 with colorectal cancer. The effect of electrical field stimulation ( EFS) was examined before nicotine was added. Finally L-NAME, a NO synthetas e inhibitor, was added before nicotine was administered again. Results: Muscle strips developed similar spontaneous resting tone. In respo nse to EFS, ulcerative colitis tissue developed lower tensions than the con trols. Nicotine significantly reduced the resting tone and peak tension aft er EFS, with a greater effect in controls. With L-NAME, peak tensions were increased more in ulcerative colitis than controls, and nicotine produced a much smaller reduction. Conclusions: Nicotine reduces circular muscle activity, predominantly throu gh the release of nitric oxide-this appears to be 'up-regulated' in active ulcerative colitis. These findings may explain some of the therapeutic bene fit from nicotine (and smoking) in ulcerative colitis and may account for t he colonic motor dysfunction in active disease.