title: Nitrite as a vascular endocrine nitric oxide reservoir that contributes to hypoxic signaling, cytoprotection, and vasodilation.
abstract: Accumulating evidence suggests that the simple and ubiquitous anion salt, nitrite (NO(2)(-)), is a physiological signaling molecule with potential roles in intravascular endocrine nitric oxide (NO) transport, hypoxic vasodilation, signaling, and cytoprotection after ischemia-reperfusion. Human and animal studies of nitrite treatment and NO gas inhalation provide evidence that nitrite mediates many of the systemic therapeutic effects of NO gas inhalation, including peripheral vasodilation and prevention of ischemia-reperfusion-mediated tissue infarction. With regard to nitrite-dependent hypoxic signaling, biochemical and physiological studies suggest that hemoglobin possesses an allosterically regulated nitrite reductase activity that reduces nitrite to NO along the physiological oxygen gradient, potentially contributing to hypoxic vasodilation. An expanded consideration of nitrite as a hypoxia-dependent intrinsic signaling molecule has opened up a new field of research and therapeutic opportunities for diseases associated with regional hypoxia and vasoconstriction.
authors.affiliation: Vascular Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1454, USA. mgladwin@nih.gov
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
authors.forename: Nicolaas J H
authors.initials: NJ
authors.lastname: Raat
authors.forename: Sruti
authors.initials: S
authors.lastname: Shiva
authors.forename: Cameron
authors.initials: C
authors.lastname: Dezfulian
authors.forename: Neil
authors.initials: N
authors.lastname: Hogg
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Kim-Shapiro
authors.forename: Rakesh P
authors.initials: RP
authors.lastname: Patel
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D019610:Cytoprotection; D004703:Endocrine System / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D006454:Hemoglobins / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000494:pharmacology*; D014664:Vasodilation / Q000502:physiology*
chemical_list: D006454:Hemoglobins; D009573:Nitrites; D009569:Nitric Oxide