What is the real physiological NO concentration in vivo?
Open accessAbstract
Clarity about the nitric oxide (NO) concentrations existing physiologically is essential for developing a quantitative understanding of NO signalling, for performing experiments with NO that emulate reality, and for knowing whether or not NO concentrations become abnormal in disease states. A decade ago, a value of about 1 microM seemed reasonable based on early electrode measurements and a provisional estimate of the potency of NO for its guanylyl cyclase-coupled receptors, which mediate physiological NO signal transduction. Since then, numerous efforts to measure NO concentrations directly using electrodes in cells and tissues have yielded an irreconcilably large spread of values. In compensation, data from several alternative approaches have now converged to provide a more coherent picture. These approaches include the quantitative analysis of NO-activated guanylyl cyclase, computer modelling based on the type, activity and amount of NO synthase enzyme contained in cells, the use of novel biosensors to monitor NO release from single endothelial cells and neurones, and the use of guanylyl cyclase as an endogenous NO biosensor in tissue subjected to a variety of challenges. All these independent lines of evidence suggest the physiological NO concentration range to be 100 pM (or below) up to approximately 5 nM, orders of magnitude lower than was once thought.
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The effects of NO in the vasculature at nM/pM concentrations are mainly mediated through activation of the canonical NO receptor sGC.
“The effects of NO in the vasculature at concentrations in the nM/pM range (397) are mainly mediated through the activation of the canonical NO receptor sGC (223, 662, 711, 751).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [397]
The paper's data in liver and blood of control wild-type mice and rats are in good agreement with previously reported values.
“Our data in liver and blood in control wild type animals (mice and rats) are in good agreement with these reports [32 - 34].”
From Skeletal muscle as an endogenous nitrate reservoir (2015) · cites this paper as [33]
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- Authors
- Hall, C. N., & Garthwaite, J.
- Affiliations
- University College London (GB)
- Corresponding author
- Garthwaite, John
- Venue
- Nitric Oxide
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 21
- Issue
- 2
- Pages
- 92-103
- ISSN
- 1089-8603 (ISSN-L)
- PMC
- PMC2779337
- OpenAlex
- W1995267843
- Cited by
- 378
- References
- 173
- Citations by year
- 2026: 19 · 2025: 22 · 2024: 16 · 2023: 23 · 2022: 16 · 2021: 19 · 2020: 19 · 2019: 8 · 2018: 19 · 2017: 26 · 2016: 25 · 2015: 30 · 2014: 24 · 2013: 30 · 2012: 29
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nitric Oxide (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (081512, 081512/Z/06/Z)
- Fondation Leducq
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
- Keywords
- no-signaling, guanylate cyclase, nitric oxide synthase, endothelial cells, neurons, nitric oxide release
- MeSH terms
- Animals, Humans, Models, Biological, Nitric Oxide, Reference Values, Signal Transduction
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