Nitrate-Nitrite-Nitric Oxide Pathway

The gaseous radical nitric oxide is involved in numerous physiologic and pathophysiological events important in anesthesiology and intensive care. Nitric oxide is endogenously generated from the amino acid l-arginine and molecular oxygen in reactions catalyzed by complex nitric oxide synthases. Recently, an alternative pathway for nitric oxide generation was discovered, wherein the inorganic anions nitrate (NO3) and nitrite (NO2), most often considered inert end products from nitric oxide generation, can be reduced back to nitric oxide and other bioactive nitrogen oxide species. This nitrate-nitrite-nitric oxide pathway is regulated differently than the classic l-arginine-nitric oxide synthase nitric oxide pathway, and it is greatly enhanced during hypoxia and acidosis. Several lines of research now indicate that the nitrate-nitrite-nitric oxide pathway is involved in regulation of blood flow, cell metabolism, and signaling, as well as in tissue protection during hypoxia. The fact that nitrate is abundant in our diet gives rise to interesting nutritional aspects in health and disease. In this article, we present an overview of this field of research with emphasis on relevance in anesthesiology and intensive care.