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Bench to bedside review: therapeutic modulation of nitric oxide in sepsis-an update.

Published version
Peer-reviewed

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Abstract

Nitric oxide is a signalling molecule with an extensive range of functions in both health and disease. Discovered in the 1980s through work that earned the Nobel prize, nitric oxide is an essential factor in regulating cardiovascular, immune, neurological and haematological function in normal homeostasis and in response to infection. Early work implicated exaggerated nitric oxide synthesis as a potentially important driver of septic shock; however, attempts to modulate production through global inhibition of nitric oxide synthase were associated with increased mortality. Subsequent work has shown that regulation of nitric oxide production is determined by numerous factors including substrate and co-factor availability and expression of endogenous regulators. In sepsis, nitric oxide synthesis is dysregulated with exaggerated production leading to cardiovascular dysfunction, bioenergetic failure and cellular toxicity whilst at the same time impaired microvascular function may be driven in part by reduced nitric oxide synthesis by the endothelium. This bench to bedside review summarises our current understanding of the ways in which nitric oxide production is regulated on a tissue and cellular level before discussing progress in translating these observations into novel therapeutic strategies for patients with sepsis.

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Keywords

Arginine, Asymmetric dimethylarginine, Citrulline, Nitric oxide, Sepsis, Septic Shock, Tetrahydrobiopterin

Journal Title

Intensive Care Med Exp

Conference Name

Journal ISSN

2197-425X
2197-425X

Volume Title

7

Publisher

Springer Science and Business Media LLC
Sponsorship
Academy of Medical Sciences (unknown)