Nitric oxide III. A molecular prelude to intestinal inflammation

Nitric oxide (NO) synthesis is markedly augmented in states of inflammation , largely due to the expression of inducible nitric oxide synthase (iNOS). Although NO has anti-inflammatory consequences under basal conditions, it r emains enigmatic as to why NO displays proinflammatory characteristics in c hronic inflammation. Either the antiinflammatory actions are weak and of li ttle consequence or, alternatively, other factors influence the role of NO in chronic inflammation. We propose that the answer to this enigma lies in the conversion of NO to other higher oxides of nitrogen (NO2, nitrogen diox ide; N2O3, dinitrogen trioxide; and ONOO-, peroxynitrite). Emerging therape utic strategies may be independent of NO synthesis; e.g., antioxidants have no direct interaction with NO but attenuate the levels and activity of hig her nitrogen oxides. Thus, whereas iNOS may be a marker for the proinflamma tory actions of NO, the species that mediate tissue injury/dysfunction in i nflammation are likely to be nitrogen oxides other than NO,