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Cited by 141Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionCardiovascular, Neuropeptides, and Oxidative Stress Research

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.

Mechanisms of Inducible Nitric Oxide Synthase–Mediated Vascular Dysfunction

Gunnett, C.A., Lund, D.D., McDowell, A.K., Faraci, F.M., Heistad, D.D.·2005·Arteriosclerosis, Thrombosis, and Vascular Biology
DOI 10.1161/01.atv.0000172626.00296.ba
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Abstract

Objective— Inducible nitric oxide synthase (iNOS) is expressed in arteries during inflammation and may contribute to vascular dysfunction. Effects of gene transfer of iNOS to carotid arteries were examined in vitro in the absence of systemic inflammation to allow examination of mechanisms by which iNOS impairs contraction and relaxation. Methods and Results— After gene transfer of iNOS with an adenovirus (AdiNOS), constrictor responses to phenylephrine (PE) and U46619 were impaired. After AdiNOS, inhibition of soluble guanylate cyclase (sGC) with 1H-[1,2,4]oxadiazolo-[4,3,2]quinoxalin-1-one (ODQ) reduced the EC 50 for PE from 4.33±0.78 μmol/L to 1.15±0.43 μmol/L (mean±SEM). These results imply that iNOS impairs contraction by activation of the NO/cGMP pathway. Relaxation to acetylcholine (ACh) also was impaired after AdiNOS. Sepiapterin (300 μmol/L), the precursor for tetrahydrobiopterin (BH 4 ), improved relaxation to Ach. Because BH 4 is an essential cofactor for production of NO by both iNOS and endothelial nitric oxide synthase (eNOS), these results suggest that iNOS may reduce production of NO by eNOS by limiting availability of BH 4 . Next, we examined effects of expression of iNOS in endothelium and adventitia. Selective expression of iNOS in endothelium, but not adventitia, impaired contraction to phenylephrine and relaxation to acetylcholine. Conclusions— We conclude that: (1) iNOS may impair contraction in part by activation of sGC; (2) iNOS impairs relaxation, at least in part, by limiting availability of BH 4 ; and (3) expression of iNOS in endothelium may be a more important mediator of vascular dysfunction than expression of iNOS in adventitia.

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Research works printed but not linked: 9

  1. 10.1161/str.27.8.1373 · DOI
  2. 10.1161/atvb.21.8.1281 · DOI
  3. 10.1161/res.34.3.317 · DOI
  4. 10.1161/hyp.33.5.1225 · DOI
  5. 2000, Physiol Res, 49, 19
  6. 1995, Mol Pharmacol, 48, 184
  7. 10.1161/atvb.17.11.2479 · DOI
  8. 1999, Proc Natl Acad Sci, 95, 9220
  9. 2004, Biochem Biophys, 41, 415

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Metadata

Authors
Gunnett, C. A., Lund, D. D., McDowell, A. K., Faraci, F. M., & Heistad, D. D.
Affiliations
University of Iowa (US)
ORCID
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2005-08
Volume
25
Issue
8
Pages
1617-1622
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
DOI
10.1161/01.atv.0000172626.00296.ba
OpenAlex
W2122779791
Semantic Scholar
57eb0f4740d865d3a49ffe67ba8b437731ac61bb
Cited by
141
References
42
Citations by year
2026: 3 · 2025: 9 · 2024: 8 · 2023: 10 · 2022: 13 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 6 · 2017: 7 · 2016: 6 · 2015: 10 · 2014: 11 · 2013: 5 · 2012: 3
FWCI
3.21
Type
journal article
Language
en
Open access
closed
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • Roy J. Carver Charitable Trust
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (HL-16066, P01HL062984, HL-62984, HL38901)
  • National Institute of Neurological Disorders and Stroke (NS24621, P01NS024621)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
  • Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
Keywords
inducible nitric oxide synthase, vascular dysfunction, gene transfer, adenoviral vector, soluble guanylate cyclase, NO-cGMP pathway, tetrahydrobiopterin, endothelial nitric oxide synthase, endothelium, adventitia, vasoconstriction, vasorelaxation, acetylcholine, phenylephrine, sepiapterin, inflammation
MeSH terms
Adenoviridae, Animals, Carotid Arteries, Carotid Artery Diseases, Endothelium, Vascular, Male, Rabbits, Vasculitis, Vasoconstriction, Vasodilation, Gene Expression Regulation, Enzymologic, Gene Transfer Techniques, Nitric Oxide Synthase Type II

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