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Nitrite as regulator of hypoxic signaling in mammalian physiology
Author(s) -
van Faassen Ernst E.,
Bahrami Soheyl,
Feelisch Martin,
Hogg Neil,
Kelm Malte,
KimShapiro Daniel B.,
Kozlov Andrey V.,
Li Haitao,
Lundberg Jon O.,
Mason Ron,
Nohl Hans,
Rassaf Tienush,
Samouilov Alexandre,
SlamaSchwok Anny,
Shiva Sruti,
Vanin Anatoly F.,
Weitzberg Eddie,
Zweier Jay,
Gladwin Mark T.
Publication year - 2009
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.20151
Subject(s) - nitric oxide , nitrite , endogeny , cytoprotection , chemistry , hypoxia (environmental) , nitrate , biochemistry , oxygen , metabolite , regulator , signal transduction , respiration , pharmacology , biology , oxidative stress , anatomy , organic chemistry , gene
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. © 2009 Wiley Periodicals, Inc. Med Res Rev, 29, No. 5, 683–741, 2009