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Cited by 94Nitric Oxide and Endothelin EffectsCardiovascular, Neuropeptides, and Oxidative Stress ResearchCardiovascular Health and Disease Prevention

Vasculoprotective Roles of Neuronal Nitric Oxide Synthase

Morishita, Tsuyoshi, Tsutsui, Masato, Shimokawa, Hiroaki, Horiuchi, Masataka, Tanimoto, Akihide, Suda, Osamu, Tasaki, Hiromi, Huang, Paul L +3 more·2002·The FASEB Journal
DOI 10.1096/fj.02-0155fje
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Abstract

Nitric oxide (NO) has multiple important actions that contribute to the maintenance of vascular homeostasis. NO is synthesized by three different isoforms of NO synthase (NOS), all of which have been reported to be expressed in human atherosclerotic vascular lesions. Although the regulatory roles of endothelial NOS (eNOS) and inducible NOS (iNOS) on the development of atherosclerosis have been described, little is known about the role of neuronal NOS (nNOS). Here, we show that nNOS also exerts important vasculoprotective effects in vivo . In a carotid artery ligation model, nNOS gene‐deficient (nNOS‐KO) mice exhibited accelerated neointimal formation and constrictive vascular remodeling caused by blood flow disruption. In a rat balloon injury model, the selective inhibition of nNOS activity potently enhanced vasoconstrictor responses to a variety of calcium‐mobilizing stimuli, suppressed tissue cGMP concentrations, a marker of vascular NO production, and exacerbated neointimal formation. In both models, nNOS was absent before injury and was up‐regulated only after the injury, and was predominantly expressed in the neointima and medial smooth muscle cells. These results provide the first direct evidence that nNOS plays important roles in suppressing arteriosclerotic vascular lesion formation in vivo .

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  • In animal models of MI, l-arginine supplementation shows mixed results, with some studies showing improvement in functional recovery and others detrimental outcomes.

    “In animal models of MI, l-arginine supplementation shows mixed results. Some studies show improvement in functional recovery (712), whereas studies in l-arginine–treated dogs show detrimental outcomes (665).”

    From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [665]

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Authors
Morishita, T., Tsutsui, M., Shimokawa, H., Horiuchi, M., Tanimoto, A., Suda, O., Tasaki, H., Huang, P. L., Sasaguri, Y., Yanagihara, N., & Nakashima, Y.
Affiliations
  • University of Occupational and Environmental Health Japan (JP)
  • Kyushu University (JP)
  • Harvard University (US)
ORCID
Venue
The FASEB Journal
Publisher
Wiley
Published
2002-10-18
Volume
16
Issue
14
Pages
1994-1996
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
DOI
10.1096/fj.02-0155fje
OpenAlex
W2098963270
Cited by
94
References
37
Citations by year
2025: 3 · 2023: 1 · 2022: 2 · 2021: 1 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 8 · 2013: 1 · 2012: 4
FWCI
3.20
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The FASEB Journal (publishedVersion)
  • PubMed (publishedVersion)
Funders
Uehara Memorial Foundation
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Keywords
neuronal nitric oxide synthase, nitric oxide, vascular protection, neointima formation, vascular remodeling, atherosclerosis, carotid artery ligation, balloon injury, vasoconstriction, cyclic GMP, smooth muscle cells, nitric oxide synthase isoforms
MeSH terms
Angioplasty, Balloon, Animals, Arterial Occlusive Diseases, Calcium, Carotid Arteries, Enzyme Inhibitors, Cyclic GMP, Ligation, Models, Biological, Vasoconstriction, Up-Regulation, Mice, Knockout, Nitric Oxide Synthase, Mice, Rats, Nitric Oxide Synthase Type I

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