BACKGROUND AND AIMS Luminal nitric oxide (NO) is greatly increased in the colon of patients with collagenous and ulcerative colitis. To define the source and consequence of enhanced NO production we have studied expression of NO synthase (NOS) isoforms and nitrotyrosine in mucosal biopsies from these patients. In addition, effects on colonic fluid transfer caused by manipulating the substrate of NOS were studied in patients with collagenous colitis.

PATIENTS Eight patients with collagenous colitis, nine with active ulcerative colitis, and 10 with uninflamed bowel were included.

RESULTS Both in collagenous and ulcerative colitis, expression of iNOS was 10²–10³ higher (p<0.001) than in uninflamed bowel and localised primarily to the epithelium. Endothelial NOS was evenly expressed in all groups while neuronal NOS was undetectable. Nitrotyrosine was markedly expressed in active ulcerative colitis but rarely detected in collagenous colitis and never in uninflamed bowel. In collagenous colitis, the output of NO_x was markedly increased compared with uninflamed bowel (283 (58)v <37 nmol/min; p<0.01) and fluid was net secreted. l-NMMA reduced the output of NO_x by 13–66% (95% confidence intervals) and secretion of fluid by 25–109% whereas l-arginine increased the output of NO_x by 3–39% and secretion of fluid by 15–93%.

CONCLUSIONS In collagenous colitis, as opposed to ulcerative colitis, upregulation of iNOS occurs in the absence of nitrotyrosine formation and mucosal damage. Excess generation of NO may be the primary cause of diarrhoea in this condition.