title: The effects of nitric oxide in acute lung injury.
abstract: Acute lung injury (ALI) is a common clinical problem associated with significant morbidity and mortality. Ongoing clinical and basic research and a greater understanding of the pathophysiology of ALI have not been translated into new anti-inflammatory therapeutic options for patients with ALI, or into a significant improvement in the outcome of ALI. In both animal models and humans with ALI, there is increased endogenous production of nitric oxide (NO) due to enhanced expression and activity of inducible NO synthase (iNOS). This increased presence of iNOS and NO in ALI contributes importantly to the pathophysiology of ALI. However, inhibition of total NO production or selective inhibition of iNOS has not been effective in the treatment of ALI. We have recently suggested that there may be differential effects of NO derived from different cell populations in ALI. This concept of cell-source-specific effects of NO in ALI has potential therapeutic relevance, as targeted iNOS inhibition specifically to key individual cells may be an effective therapeutic approach in patients with ALI. In this paper, we will explore the potential role for endogenous iNOS-derived NO in ALI. We will review the evidence for increased iNOS expression and NO production, the effects of non-selective NOS inhibition, the effects of selective inhibition or deficiency of iNOS, and this concept of cell-source-specific effects of iNOS in both animal models and human ALI.
authors.affiliation: Centre for Critical Illness Research, Lawson Health Research Institute, Division of Respirology, University of Western Ontario, London, Ontario, Canada. sanjay.mehta@lhsc.on.ca
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mehta
mesh_terms: D000208:Acute Disease; D000818:Animals; D006801:Humans; D008171:Lung Diseases / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II