Nitrite as regulator of hypoxic signaling in mammalian physiology. Med Res Rev 2009 Sep;29(5):683-741
Date
02/17/2009Pubmed ID
19219851Pubmed Central ID
PMC2725214DOI
10.1002/med.20151Scopus ID
2-s2.0-67650715561 (requires institutional sign-in at Scopus site) 370 CitationsAbstract
In this review we consider the effects of endogenous and pharmacological levels of nitrite under conditions of hypoxia. In humans, the nitrite anion has long been considered as metastable intermediate in the oxidation of nitric oxide radicals to the stable metabolite nitrate. This oxidation cascade was thought to be irreversible under physiological conditions. However, a growing body of experimental observations attests that the presence of endogenous nitrite regulates a number of signaling events along the physiological and pathophysiological oxygen gradient. Hypoxic signaling events include vasodilation, modulation of mitochondrial respiration, and cytoprotection following ischemic insult. These phenomena are attributed to the reduction of nitrite anions to nitric oxide if local oxygen levels in tissues decrease. Recent research identified a growing list of enzymatic and nonenzymatic pathways for this endogenous reduction of nitrite. Additional direct signaling events not involving free nitric oxide are proposed. We here discuss the mechanisms and properties of these various pathways and the role played by the local concentration of free oxygen in the affected tissue.
Author List
van Faassen EE, Bahrami S, Feelisch M, Hogg N, Kelm M, Kim-Shapiro DB, Kozlov AV, Li H, Lundberg JO, Mason R, Nohl H, Rassaf T, Samouilov A, Slama-Schwok A, Shiva S, Vanin AF, Weitzberg E, Zweier J, Gladwin MTAuthor
Neil Hogg PhD Sr Associate Dean, Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsHumans
Hypoxia
Nitrates
Nitric Oxide
Nitric Oxide Synthase Type III
Nitrites
Oxidation-Reduction
Oxygen
Rats
Reperfusion Injury
Signal Transduction
Vasodilation
