Induction of nitric oxide synthase in colonic smooth muscle from patients with toxic megacolon
M Mourelle1, F Casellas, F Guarner
1Digestive System Research Unit, Hospital General Vall d'Hebron, Barcelona, Spain.
Background & Aims:
Colonic inflammation may lead to motility disturbances, including severe atony. Nitric oxide is released by inflamed tissue and induces smooth muscle relaxation. The aim of this study was to analyze NO generation pathways in colonic tissue from patients who had ulcerative colitis with or without toxic megacolon and in tumor-free samples from patients with colonic neoplasm.
Methods:
Enzymatic activity was determined by transformation of [14C]arginine to [14C]citrulline in mucosa and muscular layer samples. Immunostaining of tissue sections with antibody against inducible NO synthase was investigated. The effects of endotoxin on NO synthase activity was tested in muscle strips from human colon.
Results:
Ca(2+)-independent NO synthase was undetectable or very low in muscularis propria from tumor and colitis controls. In contrast, specimens from patients with toxic megacolon had high activity (P < 0.05). Positive immunostaining for inducible NO synthase was found in muscular layers from patients with megacolon but not in tumor and colitis controls. Finally, endotoxin induced Ca(2+)-independent NO synthase activity in colonic muscle.
Conclusions:
Toxic megacolon is associated with the appearance of inducible NO synthase in the colonic muscularis propria. Local generation of excessive amounts of NO may be responsible for the colonic dilatation that is the hallmark of this syndrome.
Insights
Toxic megacolon involves increased nitric oxide (NO) production in the colon. This study found inducible NO synthase in patients with toxic megacolon, suggesting a role in colonic dilation.
Area of Science:
- Gastroenterology
- Molecular Biology
- Pathophysiology
Background:
- Colonic inflammation, as seen in ulcerative colitis, can cause motility issues like atony.
- Nitric oxide (NO), released by inflamed tissues, promotes smooth muscle relaxation.
- Understanding NO pathways is crucial for managing inflammatory bowel disease complications.
Purpose of the Study:
- To investigate nitric oxide (NO) generation pathways in colonic tissue.
- To compare NO pathways in ulcerative colitis patients (with/without toxic megacolon) and controls.
- To analyze the role of inducible NO synthase (iNOS) in toxic megacolon.
Main Methods:
- Assessed enzymatic activity of NO synthase via [14C]arginine to [14C]citrulline conversion.
- Utilized immunostaining to detect inducible NO synthase (iNOS) in tissue sections.
- Examined the effect of endotoxin on NO synthase activity in human colonic muscle strips.
Main Results:
- Ca(2+)-independent NO synthase activity was significantly higher in toxic megacolon specimens compared to controls.
- Inducible NO synthase (iNOS) was detected in the muscularis propria of patients with toxic megacolon, but not in controls.
- Endotoxin stimulation induced Ca(2+)-independent NO synthase activity in human colonic muscle.
Conclusions:
- Toxic megacolon is characterized by the presence of inducible NO synthase (iNOS) in the colonic muscularis propria.
- Elevated local NO generation may contribute to the colonic dilatation seen in toxic megacolon.
- iNOS appears to be a key player in the pathophysiology of toxic megacolon.
