Therapeutic Use of Nitric Oxide Scavengers in Shock and Sepsis

Brian   G.   Harbrecht

Abstract

Nitric oxide (NO) is a reactive radical produced by the enzyme nitric oxide synthase (NOS) and it plays an important role in a large number of biological pathways. NO can be produced under normal physiologic conditions and contribute to homeostasis but, when produced in excess, it may lead to tissue injury and organ dysfunction. The regulation of NOS activity and expression is becoming increasingly understood. NOS enzyme inhibitors as tools to decrease excessive NO synthesis have received the most attention and have been subjected to the greatest experimental study. Compounds that scavenge excessive NO have been developed and have shown promise in a number of experimental models but have received considerably less attention as potential therapeutic agents. In this article, the use of NO scavengers in two conditions in which excessive NO appears to be pathophysiologically significant, shock and sepsis, is reviewed. The relevant biology of NO in these disease states is presented and the therapeutic potential of NO scavengers in clinical care is explored.

Keywords: iNOS, Polyaminocarborylate compounds, hemorrhagic shock, endotoxin, Dithiocarbamate

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