Nitric Oxide Metabolism Linked to Sepsis

Researchers seeking new ways to treat inflammatory diseases have found that the anti-inflammatory enzyme endothelial nitric oxide synthase (eNOS) plays a second, pro-inflammatory role by facilitating expression of inducible nitric oxide synthase (iNOS), which has been linked to the development of symptoms of septic shock.

Investigators at University College (London, UK) worked with a line of mice that had been genetically engineered to lack the gene for eNOS. These animals displayed a marked reduction in iNOS production in response to bacterial endotoxin as compared to normal control mice. The experimental animals had lower plasma levels of other forms of nitric oxide synthase and fewer incidences of mortality after exposure to bacterial LPS (lipopolysaccharide) than normal mice. These findings were published in the March 18, 2005, issue of the Journal of Biological Chemistry.


"In sepsis, a systemic bacterial infection, the body expresses iNOS, which generates relatively high concentrations of nitric oxide,” explained senior author Dr. Adrian Hobbs, a researcher at University College. "This aids host defense by killing the invading organism, but in excessive quantities starts to lead to host damage. In sepsis, this is manifested predominantly as a profound hypotension, inadequate tissue perfusion, and organ failure. This often results in death. The identification of a pro-inflammatory role for eNOS-derived nitric oxide may provide the stimulus for further research in this area and thereby identify novel targets for treatment of inflammatory diseases.”



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