Cited by 1,765Nitric Oxide and Endothelin EffectsNeutrophil, Myeloperoxidase and Oxidative MechanismsAntioxidant Activity and Oxidative Stress

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Hypercholesterolemia increases endothelial superoxide anion production.

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Ohara, Y, Peterson, T E, Harrison, D G·1993·Journal of Clinical Investigation

DOI 10.1172/jci116491PMC PMC443316

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Abstract

Indirect evidence suggests accelerated degradation of endothelium-derived nitric oxide (ENDO) by superoxide anion (O2-) in hypercholesterolemic vessels (HV). To directly measure O2- production by normal vessels (NV) and HV, we used an assay for O2- based on the chemiluminescence (CL) of lucigenin (L). HV (1 mo cholesterol-fed rabbits) produced threefold more O2- than NV (1.47 +/- 0.20 nM/mg tissue/min, n = 7 vs. 0.52 +/- 0.05 nmol/mg tissue/min, n = 8, P < 0.001). Endothelial removal increased O2- production in NV (0.73 +/- 0.08, n = 6, P < 0.05), while decreasing it in HV (0.76 +/- 0.15, n = 5, P < 0.05). There was no difference between denuded HV and denuded NV. Oxypurinol, a noncompetitive inhibitor of xanthine oxidase, normalized O2- production in HV, but had no effect in NV. In separate isometric tension studies treatment with oxypurinol improved acetylcholine induced relaxations in HV, while having no effect on responses in normal vessels. Oxypurinol did not alter relaxations to nitroprusside. Thus, the endothelium is a source of O2- in hypercholesterolemia probably via xanthine oxidase activation. Increased endothelial O2- production in HV may inactivate endothelium-derived nitric oxide and provide a source for other oxygen radicals, contributing to the early atherosclerotic process.

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Self-citation
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Authors: Ohara, Y., Peterson, T. E., & Harrison, D. G.
Affiliations: Emory University (US)
ORCID: Harrison, D G
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1993-06-01
Volume: 91
Issue: 6
Pages: 2546-2551
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci116491
PMC: PMC443316
OpenAlex: W2135633069
Cited by: 1,765
References: 41
Citations by year: 2026: 3 · 2025: 7 · 2024: 10 · 2023: 9 · 2022: 15 · 2021: 21 · 2020: 29 · 2019: 29 · 2018: 18 · 2017: 30 · 2016: 26 · 2015: 28 · 2014: 43 · 2013: 43 · 2012: 47
FWCI: 26.44
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Heart Association
National Institutes of Health (5r01hl032717-09)
National Heart, Lung, and Blood Institute (R01HL039006, HL-32717, HL-39006)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Keywords: hypercholesterolemia, superoxide, endothelium, nitric oxide degradation, xanthine oxidase, oxypurinol, chemiluminescence, lucigenin, atherosclerosis, endothelial dysfunction, acetylcholine-induced relaxation, cholesterol-fed rabbits
MeSH terms: Acridines, Animals, Aorta, Cholesterol, Cholesterol, Dietary, Endothelium, Vascular, Hypercholesterolemia, Luminescent Measurements, Male, Oxypurinol, Rabbits, Superoxides, Xanthine Oxidase

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Hypercholesterolemia increases endothelial superoxide anion production.

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