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Cited by 225Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionGout, Hyperuricemia, Uric Acid

The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.

Xanthine Oxidase Inhibition Reverses Endothelial Dysfunction in Heavy Smokers

Guthikonda, Sashi, Sinkey, Christine, Barenz, Therese, Haynes, William G.·2003·Circulation
DOI 10.1161/01.cir.0000046448.26751.58
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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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Crossref · 10.1161/01.cir.0000046448.26751.58

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Research works printed but not linked: 11

  1. 10.1161/circ.88.5.8222109 · DOI
  2. 10.1161/circ.89.4.8149547 · DOI
  3. 10.1161/circ.100.11.1161 · DOI
  4. 10.1161/hyp.30.1.57 · DOI
  5. 10.1161/hyp.35.3.746 · DOI
  6. 1982, Eur J Clin Pharmacol, 22, 77
  7. 10.1161/circ.92.3.357 · DOI
  8. 1996, Am J Physiol, 270, L941
  9. 10.1161/res.76.3.388 · DOI
  10. 1989, Am J Physiol, 257, H1640
  11. 10.1161/atvb.22.1.28 · DOI

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Metadata

Authors
Guthikonda, S., Sinkey, C., Barenz, T., & Haynes, W. G.
Affiliations
University of Iowa (US)
ORCID
Haynes, William G.
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2003-01-28
Volume
107
Issue
3
Pages
416-421
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/01.cir.0000046448.26751.58
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 (medical) › 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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