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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), pp. 683-741. (doi:10.1002/med.20151). (PMID:19219851).

Record type: Article


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

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e-pub ahead of print date: 13 February 2009
Published date: September 2009
Organisations: Clinical & Experimental Sciences


Local EPrints ID: 337704
ISSN: 0198-6325
PURE UUID: 59e1a649-5691-4931-9109-13415328dbea
ORCID for Martin Feelisch: ORCID iD

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Date deposited: 02 May 2012 13:57
Last modified: 18 Jul 2017 06:01

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Author: Ernst E. van Faassen
Author: Soheyl Bahrami
Author: Martin Feelisch ORCID iD
Author: Neil Hogg
Author: Malte Kelm
Author: Daniel B. Kim-Shapiro
Author: Andrey V. Kozlov
Author: Haitao Li
Author: Jon O. Lundberg
Author: Ron Mason
Author: Hans Nohl
Author: Tienush Rassaf
Author: Alexandre Samouilov
Author: Anny Slama-Schwok
Author: Sruti Shiva
Author: Anatoly F. Vanin
Author: Eddie Weitzberg
Author: Jay Zweier
Author: Mark T. Gladwin

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