Nitrite as regulator of hypoxic signaling in mammalian physiology

van Faassen, Ernst E., Bahrami, Soheyl, Feelisch, Martin, Hogg, Neil, Kelm, Malte, Kim-Shapiro, Daniel B., Kozlov, Andrey V., Li, Haitao, Lundberg, Jon O., Mason, Ron, Nohl, Hans, Rassaf, Tienush, Samouilov, Alexandre, Slama-Schwok, Anny, Shiva, Sruti, Vanin, Anatoly F., Weitzberg, Eddie, Zweier, Jay and Gladwin, Mark T. (2009) Nitrite as regulator of hypoxic signaling in mammalian physiology. Medicinal Research Reviews, 29, (5), 683-741. (doi:10.1002/med.20151). (PMID:19219851).


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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

Item Type: Article
Digital Object Identifier (DOI): doi:10.1002/med.20151
ISSNs: 0198-6325 (print)
1098-1128 (electronic)
Subjects: Q Science > QP Physiology
R Medicine > R Medicine (General)
Divisions : Faculty of Medicine > Clinical and Experimental Sciences
ePrint ID: 337704
Accepted Date and Publication Date:
13 February 2009Made publicly available
September 2009Published
Date Deposited: 02 May 2012 13:57
Last Modified: 31 Mar 2016 14:27

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