Nitric Oxide Ways in Sepsis

Abstract

Nitric oxide (NO) is a short-lived radical element involved in the regulation of a large number of physiological functions under normal or pathological conditions. It is produced by NO synthase (NOS) from L-arginine. During septic conditions, NO production is greatly increased due to an over-expression of an inducible form of NOS. In these conditions, NO could be responsible for a direct toxicity on many organs. An indirect harmful effect could be due to nitrosylation of cellular proteins and peroxynitrite production. These products induce an inhibition of the respiratory chain and therefore a direct mitochondrial toxicity. NO induces micro-and macro-vascular, myocardial, immune and neuronal dysfunctions.

The few available studies in human beings, using pharmacological non-specific antagonists of NO, resulted in failure or deleterious effect. This highlights the complexity of pathways related to NO and the need for a better understanding of its involvement in the pathogenesis of organ failure in order to develop better targeted therapies.