Role of nitric oxide in inflammation and tissue injury during endotoxemia and hemorrhagic shock

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.