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 remains enigmatic as to why NO displays proinflammatory characteristics in chronic inflammation. Either the anti-inflammatory actions are weak and of little 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 dioxide; N2O3, dinitrogen trioxide; and ONOO-, peroxynitrite). Emerging therapeutic strategies may be independent of NO synthesis; e.g., antioxidants have no direct interaction with NO but attenuate the levels and activity of higher nitrogen oxides. Thus, whereas iNOS may be a marker for the proinflammatory actions of NO, the species that mediate tissue injury/dysfunction in inflammation are likely to be nitrogen oxides other than NO.
Miller
M J
MJ
Department of Pediatrics, Albany Medical College, Albany, New York 12208, USA. mark_miller@cgateway.amc.edu
Sandoval
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015415:Biomarkers / Q000032:analysis; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000503:physiopathology*; D007422:Intestines / Q000503:physiopathology*; D008954:Models, Biological; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009589:Nitrogen Oxides / Q000633:toxicity; D011247:Pregnancy
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D009566:Nitrates; D009589:Nitrogen Oxides; C039642:peroxynitric acid; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II