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

Since the discovery that nitric oxide ((NO)-N-.) 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)-N-. as a possible mediator of the severe hypotension and impaired vasoreactivity characteristic of circulatory failure. Given the ubiquitous and complex role of (NO)-N-. in biologic systems, inhibition of (NO)-N-. synthesis in experimental and clinical studies of shock has yielded mixed, sometimes contradictory, results. Although overproduction of (NO)-N-. in the vasculature may result in systemic vasodilatation,(NO)-N- . 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)-N-. in septic shock and hemorrhagic shock is discussed, and novel therapeutic strategies for manipulation of (NO)-N-. formation are examined.