Temporal distribution of neuronal and inducible nitric oxide synthase and nitrotyrosine during colitis in rats

Nitric oxide (NO) has been implicated in the pathogenesis of inflammatory b owel disease since increased NO production is observed in this disease. NO can react with superoxide to generate peroxynitrite which causes and/or exa cerbates colitis. Peroxynitrite, in turn, nitrates tyrosine residues to for m nitrotyrosine which can be identified immunohistochemically. We investiga ted the distribution of neuronal and inducible nitric oxide synthase (iNOS) and nitrotyrosine over time in experimental colitis. Colitis was induced b y intracolonic administration of trinitrobenzene sulphonic acid (TNBS) in r ats. Animals were killed 1, 2, 7 and 14 days after treatment. Myeloperoxida se activity was used as an index of inflammation, and tissues were examined using immunohistochemistry. Neuronal NOS immunoreactivity was present thro ughout the colon, and was only slightly reduced 1 day after the induction o f colitis. Conversely, iNOS immunoreactivity almost absent in controls dram atically increased in the mucosa and submucosa at the early stages of infla mmation. iNOS was present in monocytes and macrophages and also another uni dentified cell type. Seven and 14 days after the induction of colitis, iNOS was also found in nerves in the circular muscle and in the myenteric plexu s. Nitrotyrosine immunoreactivity present in a few cells in the normal muco sa also increased 1 day after the induction of colitis and decreased therea fter. The pattern of distribution of nitrotyrosine immunoreactivity was dis tinct from that of iNOS. The increase of iNOS expression at the early stage of inflammation may play a role in causing tissue injury via peroxynitrite formation. The expression of iNOS seen in the enteric nerves in the later stage of inflammation correlates temporally with the beginning of tissue re pair and with the re-innervation and compensatory growth of nerves. NO may potentially play a physiological as well as pathological role in experiment al colitis.