Changes in distribution of three isoforms of nitric oxide synthase in ulcerative colitis

Background: Nitric oxide (NO) has an important role both in normal physiology and pathological events of the colon. Our aim was to study possible changes of the three nitric oxide synthases in ulcerative colitis (UC). Methods: Tissue samples from normal colon and least and moderately affected regions of ulcerative colitis colon were obtained at surgery and immunostained for NOS-1, NOS-2, NOS-3, and GAP-43, a marker of nerve fibers. Quantitative analysis of NOS-1 immunoreactivity was performed on the circular muscle layer. Results: NOS-1-immunoreactive fibers in the muscularis mucosae disappeared in least affected and moderately affected UC colon. Quantitative analysis of NOS-1-immunoreactive nerve fibers in the circular muscle showed no differences between normal and diseased colon. NOS-2 immunoreactivity appeared apically in the epithelial cells. In normal colon some specimens showed immunoreactivity in lower parts of crypts. NOS-2 immunoreactivity increased according to the severity of UC. NOS-3 immunoreactivity was exclusively localized in the vascular endothelium. The difference in NOS-3 staining intensity between the lamina propria and submucosa observed in normal tissue disappeared in moderately affected UC colon. The number of NOS-3-immunoreactive vascular profiles increased in the lamina propria of UC colon. Conclusions: All three NOS isoforms show specific changes in UC colon.