Enhanced colonic nitric oxide generation and nitric oxide synthase activity in ulcerative colitis and Crohn's disease

• Published in: Gut Vol. 36; no. 5; pp. 718 - 723
• Main Authors: Rachmilewitz, D, Stamler, J S, Bachwich, D, Karmeli, F, Ackerman, Z, Podolsky, D K
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.05.1995; BMJ; BMJ Publishing Group LTD
• Subjects: Adult; Amino Acid Oxidoreductases - metabolism; Biological and medical sciences; Calcium - metabolism; Colitis, Ulcerative - metabolism; Colon - drug effects; Colon - metabolism; Crohn Disease - metabolism; Culture Techniques; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Isoenzymes; Male; Medical sciences; Methylprednisolone - pharmacology; Nitric Oxide - biosynthesis; Nitric Oxide Synthase; Other diseases. Semiology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Human; Enzyme; Secretion; Synthase; Inflammatory disease; Crohn disease; Microbiological investigation; Enzymatic activity; Nitrogen monoxide; Digestive diseases; Intestinal disease; Colon; Ulcerative colitis
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.36.5.718

Recent studies have suggested that nitric oxide (NO.), the product of nitric oxide synthase in inflammatory cells, may play a part in tissue injury and inflammation through its oxidative metabolism. In this study the colonic generation of oxides of nitrogen (NOx) and nitric oxide synthase activity was determined in ulcerative colitis and Crohn's disease. Colonic biopsy specimens were obtained from inflammatory bowel disease patients and from normal controls. Mucosal explants were cultured in vitro for 24 hours and NOx generation was determined. Nitric oxide synthase activity was monitored by the conversion of [3H]-L-arginine to citrulline. Median NOx generation by inflamed colonic mucosa of patients with active ulcerative colitis and Crohn's colitis was 4.2- and 8.1-fold respectively higher than that by normal human colonic mucosa. In ulcerative colitis and Crohn's colitis nitric oxide synthase activity was 10.0- and 3.8-fold respectively higher than in normal subjects. Colonic NOx generation is significantly decreased by methylprednisolone and ketotifen. The decrease in NOx generation by cultured colonic mucosa induced by methylprednisolone suggests that NO synthase activity is induced during the culture and the steroid effect may contribute to its therapeutic effect. Enhanced colonic NOx generation by stimulated nitric oxide synthase activity in ulcerative colitis and Crohn's disease may contribute to tissue injury.