Xanthine Oxidase Inhibition Reverses Endothelial Dysfunction in Heavy Smokers
Abstract
Background— Cigarette smoking causes endothelial dysfunction, possibly through increased oxidant stress. The enzyme xanthine oxidase produces oxidative free radicals. We tested the hypothesis that xanthine oxidase contributes to endothelial dysfunction in cigarette smokers by administering the inhibitor allopurinol. Methods and Results— Fourteen cigarette smokers (31±4 pack years) and 14 age- and sex-matched healthy non-smoking control subjects participated in a single-blinded, randomized, 2-phase crossover study. All subjects had no other risk factors for atherosclerosis. Inhibition of xanthine oxidase was achieved by a single oral dose of 600 mg of allopurinol on the day of the study. Stimulated nitric oxide endothelial responses were assessed by forearm blood flow responses to intraarterial administration of acetylcholine and bradykinin 4 to 7 hours later; basal nitric oxide was assessed using the nitric oxide synthase inhibitor NG-monomethyl- l -arginine (L-NMMA); and nitroprusside was used to assess sensitivity to nitric oxide. Dilatation produced by acetylcholine was significantly less in smokers (254±57%) than healthy controls (390±55%) ( P =0.009). Allopurinol reversed endothelial dysfunction in smokers (acetylcholine, 463±78%, P =0.001) without affecting responses in non-smokers (401±80%). Bradykinin responses were also impaired in smokers ( P =0.003), and improved with allopurinol, though not significantly ( P =0.06). Responses to nitroprusside and L-NMMA were not significantly different between smokers and controls and were not altered by allopurinol. Conclusions— Smoking-induced endothelial dysfunction of resistance vessels is rapidly reversed with oral allopurinol. These data suggest that xanthine oxidase contributes importantly to endothelial dysfunction caused by cigarette smoking.
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Amelioration of endothelial function in smokers was observed with allopurinol/oxypurinol.
“Amelioration of endothelial function in smokers was also observed (387).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [387]
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- Authors
- Guthikonda, S., Sinkey, C., Barenz, T., & Haynes, W. G.
- Affiliations
- University of Iowa (US)
- ORCID
- Haynes, William G.
- Venue
- Circulation
- Published
- 2003-01-28
- Volume
- 107
- Issue
- 3
- Pages
- 416-421
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2033870657
- Cited by
- 225
- References
- 35
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2023: 7 · 2022: 7 · 2021: 15 · 2020: 3 · 2019: 11 · 2018: 14 · 2017: 11 · 2016: 8 · 2015: 9 · 2014: 12 · 2013: 9 · 2012: 8
- FWCI
- 8.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-55006, P50HL055006, HL58972, R01HL058972)
- National Institute of Neurological Disorders and Stroke (NS55105)
- National Center for Research Resources (RR 00059, M01RR000059)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
- Keywords
- xanthine oxidase, allopurinol, endothelial dysfunction, cigarette smoking, nitric oxide, acetylcholine-induced vasodilation, bradykinin, forearm blood flow, oxidative stress, resistance vessels, smokers
- MeSH terms
- Adolescent, Adult, Aged, Allopurinol, Endothelium, Vascular, Enzyme Inhibitors, Female, Forearm, Humans, Male, Middle Aged, Regional Blood Flow, Smoking, Vasodilation, Xanthine Oxidase, Single-Blind Method, Cross-Over Studies, Nitric Oxide Synthase, omega-N-Methylarginine
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