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01-03-2015 | Commentary

Nitrite: On the Journey from Toxin to Therapy

Authors: Arlin B. Blood, Gordon G. Power

Published in: Clinical Pharmacokinetics | Issue 3/2015

Excerpt

Biomedical interest in the nitrite anion (NO₂ ⁻) was once limited primarily to its toxic effects following ingestion of contaminated food or well water. The discovery that nitric oxide (NO) is an endogenously produced signaling molecule, and that nitrite is a relatively stable product of NO metabolism, brought increased focus on nitrite concentrations as an index of endogenous NO production. More recently, however, it has become apparent that nitrite is more than just a byproduct of NO, but that it can also be converted back into NO by a number of different biochemical pathways (see the recent review by Lundberg and Weitzberg [1]). As a result, nitrite is now widely regarded as a bioactive molecule with potentially wide-ranging physiological function and therapeutic application. …

Lundberg JO, Weitzberg E. NO-synthase independent NO generation in mammals. Biochem Biophys Res Commun. 2010;396(1):39–45.CrossRefPubMed

Rhodes P, Leone AM, Francis PL, Struthers AD, Moncada S, Rhodes PM. The l-arginine: nitric oxide pathway is the major source of plasma nitrite in fasted humans. Biochem Biophys Res Commun. 1995;209(2):590–6.CrossRefPubMed

Kim-Shapiro DB, Gladwin MT. Mechanisms of nitrite bioactivation. Nitric Oxide. 2014;30(38):58–68.CrossRef

Hunter CJ, Dejam A, Blood AB, Shields H, Kim-Shapiro DB, Machado RF, et al. Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator. Nat Med. 2004;10(10):1122–7.CrossRefPubMed

Blood AB, Schroeder HJ, Terry MH, Merrill-Henry J, Bragg SL, Vrancken K, et al. Inhaled nitrite reverses hemolysis-induced pulmonary vasoconstriction in newborn lambs without blood participation. Circulation. 2011;123(6):605–12.CrossRefPubMedCentralPubMed

Ingram TE, Pinder AG, Bailey DM, Fraser AG, James PE. Low-dose sodium nitrite vasodilates hypoxic human pulmonary vasculature by a means that is not dependent on a simultaneous elevation in plasma nitrite. Am J Physiol. 2010;298(2):H331–9.

Rix PJ, Vick A, Attkins NJ, Barker GE, Bott AW, Alcorn H, Jr., et al. Pharmacokinetics, pharmacodynamics, safety, and tolerability of nebulized sodium nitrite (AIR001) following repeat-dose inhalation in healthy subjects. Clin Pharmacokinet. 2014. doi:10.1007/s40262-014-0201-y.

Rassaf T, Ferdinandy P, Schulz R. Nitrite in organ protection. Br J Pharmacol. 2014;171(1):1–11.CrossRefPubMedCentralPubMed

Title: Nitrite: On the Journey from Toxin to Therapy
Authors: Arlin B. Blood
Gordon G. Power
Publication date: 01-03-2015
Publisher: Springer International Publishing
Published in: Clinical Pharmacokinetics / Issue 3/2015
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-014-0231-5

At a glance: The STEP trials

Springer Medicine

Nitrite: On the Journey from Toxin to Therapy

Excerpt

At a glance: The STEP trials

Springer Medicine

Excerpt

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