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
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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“neuronal NOS (nNOS) and inducible NOS (iNOS) can provide compensatory NO generation or exacerbated RNS synthesis”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [386]
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Enzymatic function of nitric oxide synthases
Andrew, P. (1999) · Cardiovascular Research · doi:10.1016/s0008-6363(99)00115-7 · Cited by 776
BIOSYNTHESIS AND METABOLISM OF TETRAHYDROBIOPTERIN AND MOLYBDOPTERIN
Nichol, C. A., Smith, G. K., & Duch, D. S. (1985) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.54.070185.003501 · Cited by 558
Regulation of Endothelial Nitric Oxide Synthase by Tetrahydrobiopterin in Vascular Disease
Alp, N. J., & Channon, K. M. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000110785.96039.f6 · Cited by 536
Regulation of Nitric Oxide-Sensitive Guanylyl Cyclase
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Oxidation of Tetrahydrobiopterin by Peroxynitrite: Implications for Vascular Endothelial Function
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Expression of Multiple Isoforms of Nitric Oxide Synthase in Normal and Atherosclerotic Vessels
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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)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2005-08
- Volume
- 25
- Issue
- 8
- Pages
- 1617-1622
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- 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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