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Cited by 313Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionEicosanoids and Hypertension Pharmacology

Endothelium-derived nitric oxide and vascular physiology and pathology

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Arnal, J.-F., Dinh-Xuan, A.-T., Pueyo, M., Darblade, B., Rami, J.·1999·Cellular and Molecular Life Sciences
DOI 10.1007/s000180050358PMC PMC11146781
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Abstract

In 1980, Furchgott and Zawadzki demonstrated that the relaxation of vascular smooth muscle cells in response to acetylcholine is dependent on the anatomical integrity of the endothelium. Endothelium-derived relaxing factor was identified 7 years later as the free radical gas nitric oxide (NO). In endothelium, the amino acid L-arginine is converted to L-citrulline and NO by one of the three NO synthases, the endothelial isoform (eNOS). Shear stress and cell proliferation appear to be, quantitatively, the two major regulatory factors of eNOS gene expression. However, eNOS seems to be mainly regulated by modulation of its activity. Stimulation of specific receptors to various agonists (e.g., bradykinin, serotonin, adenosine, ADP/ATP, histamine, thrombin) increases eNOS enzymatic activity at least in part through an increase in intracellular free Ca2+. However, the mechanical stimulus shear stress appears again to be the major stimulus of eNOS activity, although the precise mechanisms activating the enzyme remain to be elucidated. Phosphorylation and subcellular translocation (from plasmalemmal caveolae to the cytoskeleton or cytosol) are probably involved in these regulations. Although eNOS plays a major vasodilatory role in the control of vasomotion, it has not so far been demonstrated that a defect in endothelial NO production could be responsible for high blood pressure in humans. In contrast, a defect in endothelium-dependent vasodilation is known to be promoted by several risk factors (e.g., smoking, diabetes, hypercholesterolemia) and is also the consequence of atheroma (fatty streak infiltration of the neointima). Several mechanisms probably contribute to this decrease in NO bioavailability. Finally, a defect in NO generation contributes to the pathophysiology of pulmonary hypertension. Elucidation of the mechanisms of eNOS enzyme activity and NO bioavailability will contribute to our understanding the physiology of vasomotion and the pathophysiology of endothelial dysfunction, and could provide insights for new therapies, particularly in hypertension and atherosclerosis.

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  • Therapeutic use of inorganic nitrite may be of widespread benefit given the reciprocal relationship between nitrite and NO plus the fact that NO bioavailability contributes to numerous disease states.

    “However, given the appreciation of the reciprocal relationship between nitrite and NO plus the fact that NO bioavailability is well known to contribute to numerous disease states [136, 137], therapeutic use of inorganic nitrite may be of widespread benefit.”

    From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [136]

  • Therapeutic use of inorganic nitrite may be of widespread benefit given the reciprocal relationship between nitrite and NO plus the fact that NO bioavailability contributes to numerous disease states.

    “However, given the appreciation of the reciprocal relationship between nitrite and NO plus the fact that NO bioavailability is well known to contribute to numerous disease states [136, 137], therapeutic use of inorganic nitrite may be of widespread benefit.”

    From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [137]

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  1. 60 White C. R., Brock T. A., Chang L. Y., Crapo J., Briscoe P., Ku D. et al. (1994) Superoxide and peroxynitrite in atherosclerosis. Proc. Natl. Acad. Sci. USA 91: 1044-1048

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Authors
Arnal, J.-F., Dinh-Xuan, A.-T., Pueyo, M., Darblade, B., & Rami, J.
Affiliations
Inserm (FR)
ORCID
Arnal, J.-F.
Venue
Cellular and Molecular Life Sciences
Publisher
Springer Science and Business Media LLC
Published
1999
Volume
55
Issue
9
Pages
1078
ISSN
1420-682X (ISSN-L)
DOI
10.1007/s000180050358
PMC
PMC11146781
OpenAlex
W2093217834
Cited by
313
References
79
Citations by year
2026: 3 · 2025: 7 · 2024: 6 · 2023: 6 · 2022: 4 · 2021: 1 · 2020: 5 · 2019: 12 · 2018: 4 · 2017: 9 · 2016: 10 · 2015: 16 · 2014: 13 · 2013: 8 · 2012: 15
FWCI
6.04
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Cellular and Molecular Life Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Keywords
nitric oxide, endothelium-derived relaxing factor, endothelial nitric oxide synthase, shear stress, endothelial dysfunction, NO bioavailability, endothelium-dependent vasodilation, vasomotion, hypertension, atherosclerosis, pulmonary hypertension, L-arginine, intracellular calcium, eNOS phosphorylation, subcellular translocation
MeSH terms
Animals, Arginine, Arteriosclerosis, Blood Vessels, Cell Adhesion, Endothelium, Vascular, Enzyme Induction, Enzyme Inhibitors, Humans, Hypertension, Hypertension, Pulmonary, Isoenzymes, Membrane Proteins, Nitric Oxide, Rabbits, Vascular Diseases, Vasodilation, Signal Transduction, Oxidative Stress, Nitric Oxide Synthase, omega-N-Methylarginine, NG-Nitroarginine Methyl Ester, Caveolins, Caveolin 1, Nitric Oxide Synthase Type III

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