Cited by 296Nitric Oxide and Endothelin EffectsMitochondrial Function and PathologyRedox biology and oxidative stress

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On the mechanism by which vascular endothelial cells regulate their oxygen consumption

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Clementi, Emilio, Brown, Guy Charles, Foxwell, Neale, Moncada, Salvador·1999·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.96.4.1559PMC PMC15516

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Abstract

Two enzymes, soluble guanylyl cyclase and cytochrome c oxidase, have been shown to be exquisitely sensitive to nitric oxide (NO) at low physiological concentrations. Activation of the soluble guanylyl cyclase by endogenous NO and the consequent increase in the second messenger cyclic GMP are now known to control a variety of biological functions. Cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, is inhibited by NO. However, it is not clear whether NO produced by the constitutive NO synthase interacts with cytochrome c oxidase, nor is it known what the biological consequences of such an interaction might be. We now show that NO generated by vascular endothelial cells under basal and stimulated conditions modulates the respiration of these cells in response to acute changes in oxygen concentration. This action occurs at the cytochrome c oxidase and depends on influx of calcium. Thus, NO plays a physiological role in adjusting the capacity of this enzyme to use oxygen, allowing endothelial cells to adapt to acute changes in their environment.

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Authors: Clementi, E., Brown, G. C., Foxwell, N., & Moncada, S.
Affiliations: University College London (GB)
ORCID: Clementi, Emilio
Brown, Guy Charles
Moncada, Salvador
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1999-02-16
Volume: 96
Issue: 4
Pages: 1559-1562
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.96.4.1559
PMC: PMC15516
OpenAlex: W2067637944
Cited by: 296
References: 38
Citations by year: 2026: 1 · 2025: 4 · 2024: 5 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 8 · 2015: 9 · 2014: 8 · 2013: 11 · 2012: 7
FWCI: 14.54
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
UCL Discovery (University College London) (submittedVersion)
Funders: Wellcome Trust
Consiglio Nazionale delle Ricerche
Directorate for Biological Sciences
Biotechnology and Biological Sciences Research Council
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords: nitric oxide, vascular endothelial cells, oxygen consumption, cytochrome c oxidase, soluble guanylate cyclase, cyclic GMP, nitric oxide synthase, mitochondrial respiration, calcium influx, oxygen sensing
MeSH terms: Animals, Aorta, Thoracic, Bradykinin, Calcium, Cells, Cultured, Egtazic Acid, Endothelium, Vascular, Nitric Oxide, Oxygen Consumption, Swine, omega-N-Methylarginine, NG-Nitroarginine Methyl Ester

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On the mechanism by which vascular endothelial cells regulate their oxygen consumption

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