| Role of Nitric Oxide in Inflammation and Tissue Injury during Endotoxemia and Hemorrhagic Shock Nishit S. Shah and Timothy R. Billiar Department of Surgery, University of Pittsburgh,
Pittsburgh, Pennsylvania Abstract
Since the discovery that nitric oxide (·NO) accounts for the biologic activity of endothelial-derived relaxing factor, a torrent of research over the last decade has focused on its role, protective or detrimental, in myriad pathophysiologic conditions. Recently, increasing attention has focused on ·NO as a possible mediator of the severe hypotension and impaired vasoreactivity characteristic of circulatory failure. Given the ubiquitous and complex role of ·NO in biologic systems, inhibition of ·NO synthesis in experimental and clinical studies of shock has yielded mixed, sometimes contradictory, results. Although overproduction of ·NO in the vasculature may result in systemic vasodilatation, ·NO synthesis has also clearly been shown to have a beneficial role in regulating organ perfusion and mediating cytotoxicity. In this review, the pathophysiologic importance of ·NO in septic shock and hemorrhagic shock is discussed, and novel therapeutic strategies for manipulation of ·NO formation are examined. -- Environ Health Perspect 106(Suppl 5) :1139-1143 (1998) . http://ehpnet1.niehs.nih.gov/docs/1998/Suppl-5/1139-1143shah/abstract.html Key words: nitric oxide, inducible nitric oxide synthase, sepsis, hemorrhagic shock
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