EXPRESSION, ACTIVITY AND CELLULAR-LOCALIZATION OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN RAT ILEUM AND COLON POSTIRRADIATION

Purpose: Studies were conducted to determine the acute effect of expos ure to ionizing radiation on inducible nitric oxide synthase (iNOS) ac tivity and expression in the rat ileum and colon. Materiais and Method s: Rats received whole body exposure to 10 Gy gamma-radiation and were studied 0.5-48 h later. Segments of ileum and colon were taken from a naesthetized rats for determination of myeloperoxidase activity (a mar ker of acute inflammation), and iNOS mRNA expression, enzyme activity and localization. Results: Myeloperoxidase activity in ileum was not i ncreased compared with shams until 48 h post-irradiation. In colon, my eloperoxidase activity was lower than shams at 48 h postirradiation. I rradiation resulted in a dexamethasone-sensitive expression of iNOS mR NA in both the ileum and colon within 2 h. Inducible NOS activity was significantly elevated in the ileum, but not in the colon. The elevate d ileal nitric oxide synthase activity was significantly reduced by pr etreatment with the iNOS inhibitor, aminoguanidine. Immunoreactivity f or iNOS protein was localized to the epithelium and was apparent at 2- 6 h post-irradiation in the ileum, bur not the colon. Conclusions: Exp osure to ionizing radiation results in the expression of iNOS in ileum and colon, bur only significantly increases iNOS activity in the ileu m. Inducible NOS-derived NO may participate in acute, whole body radia tion-induced ileal dysfunction, independently of the development of an inflammatory response.