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Oxidative Stress and Endothelial Dysfunction in Aortas of Aged Spontaneously Hypertensive Rats by NOX1/2 Is Reversed by NADPH Oxidase Inhibition
Open accessAbstract
Arterial hypertension is associated with increased levels of reactive oxygen species, which may scavenge endothelium-derived NO and thereby diminish its vasorelaxant effects. However, the quantitatively relevant source of reactive oxygen species is unclear. Thus, this potential pathomechanism is not yet pharmacologically targetable. Several enzymatic sources of reactive oxygen species have been suggested: uncoupled endothelial NO synthase, xanthine oxidase, and NADPH oxidases. Here we show that increased reactive oxygen species formation in aortas of 12- to 14-month–old spontaneously hypertensive rats versus age-matched Wistar Kyoto rats is inhibited by the specific NADPH oxidase inhibitor VAS2870 but neither by the xanthine oxidase inhibitor oxypurinol nor the NO synthase inhibitor N G -nitro- l -arginine methyl ester. NADPH oxidase activity, as well as protein expression of its catalytic subunits, NOX1 and NOX2, was increased in the aortas of spontaneously hypertensive rats, whereas the expression of NOX4 protein, the most abundant NOX isoform, was not significantly changed. Impaired acetylcholine-induced relaxation of spontaneously hypertensive rat aortas was significantly improved by VAS2870. In conclusion, NOX1 and NOX2 but not NOX4 proteins are increased in aged spontaneously hypertensive rat aortas. Importantly, these NOX isoforms, in particular, ectopic expression of NOX1 in endothelial cells, appear to affect vascular function in an NADPH oxidase inhibitor-reversible manner. NADPH oxidases may, thus, be a novel target for the treatment of systemic hypertension.
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“One study has related NOX4 to hyperglycemia and insulin resistance in mice (1012).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [1012]
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Metadata
- Authors
- Wind, S., Beuerlein, K., Armitage, M. E., Taye, A., Kumar, A. H. S., Janowitz, D., Neff, C., Shah, A. M., Wingler, K., & Schmidt, H. H. H. W.
- Affiliations
- King's College London (GB)
- Venue
- Hypertension
- Published
- 2010-09
- Volume
- 56
- Issue
- 3
- Pages
- 490-497
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2116462934
- Cited by
- 181
- References
- 56
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 10 · 2021: 6 · 2020: 7 · 2019: 13 · 2018: 5 · 2017: 11 · 2016: 13 · 2015: 23 · 2014: 18 · 2013: 13 · 2012: 23
- FWCI
- 11.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Research Portal (King's College London) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- British Heart Foundation (RG/08/011/25922)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- NADPH oxidase, NOX1, NOX2, NOX4, oxidative stress, endothelial dysfunction, spontaneously hypertensive rats, hypertension, aging, reactive oxygen species, VAS2870, acetylcholine-induced relaxation, endothelial nitric oxide, xanthine oxidase, endothelial nitric oxide synthase, aorta
- MeSH terms
- NADPH Oxidase 1, NADPH Oxidase 2, Acetylcholine, Aging, Analysis of Variance, Animals, Aorta, Endothelium, Vascular, Fluorescent Antibody Technique, Hypertension, Male, Membrane Glycoproteins, NADH, NADPH Oxidoreductases, Rats, Inbred SHR, Rats, Inbred WKY, Xanthine Oxidase, Blotting, Western, Reactive Oxygen Species, Oxidative Stress, NADPH Oxidases, Rats, Nitric Oxide Synthase Type III
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