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Measurement of in vivo nitric oxide synthesis in humans using stable isotopic methods: a systematic review

Siervo, M., Stephan, B.C.M., Feelisch, M. and Bluck, L.J.C (2011) Measurement of in vivo nitric oxide synthesis in humans using stable isotopic methods: a systematic review Free Radical Biology & Medicine, 51, (4), pp. 795-804. (doi:10.1016/j.freeradbiomed.2011.05.032). (PMID:21672626).

Record type: Article


Stable isotopic methods are considered the "gold standard" for the measurement of rates of in vivo NO production. However, values reported for healthy human individuals differ by more than 1 order of magnitude. The reason for the apparent variability in NO production is unclear. The primary aim of this review was to evaluate and compare the rates of in vivo NO production in health and disease using stable isotope methods. Articles were retrieved using the PubMed electronic database. Information on concentrations, isotopic enrichments of fluxes, and conversion rates of molecules involved in the NO metabolic pathway was extracted from selected articles; 35 articles were included in the final analysis. Three protocols were identified, including the arginine-citrulline, the arginine-nitrate, and the oxygen-nitrate protocols. The arginine-citrulline protocol showed a wider variability compared to the arginine-nitrate and oxygen-nitrate protocols. The direction of the association between disease state and rate of NO production was essentially determined by the etiopathogenesis of the disorder (inflammatory, metabolic, vascular). Considerable variation in methodologies used to assess whole-body NO synthesis in humans exists. The precision of several aspects of the techniques and the validity of some assumptions made remain unknown, and there is a paucity of information about physiological rates of NO production from childhood over adolescence to old age.

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e-pub ahead of print date: 3 June 2011
Published date: 15 August 2011
Organisations: Clinical & Experimental Sciences


Local EPrints ID: 337693
ISSN: 0891-5849
PURE UUID: 7dc80365-32d7-4381-a0c9-5c7169acb93b
ORCID for M. Feelisch: ORCID iD

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Date deposited: 02 May 2012 11:31
Last modified: 18 Jul 2017 06:01

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Author: M. Siervo
Author: B.C.M. Stephan
Author: M. Feelisch ORCID iD
Author: L.J.C Bluck

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