Evidence map›Paper›PMID 8710942›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America1996

Circulating plasma xanthine oxidase contributes to vascular dysfunction in hypercholesterolemic rabbits.

C R White, V Darley-Usmar, W R Berrington, M McAdams, J Z Gore, J A Thompson, D A Parks, M M Tarpey, B A Freeman

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
8.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

75 citing papers in PubMed, 372 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Regulation of nitric oxide generation and consumption.International journal of biological sciences · 2025
    Review
  4. Article
  5. Review
  6. Effects of superoxide anion attack on the lipoprotein HDL.Molecular and cellular biochemistry · 2023
    Article
  7. Article
  8. Article
  9. Review
  10. Superoxide-induced Type I collagen secretion depends on prolyl 4-hydroxylases.Biochemical and biophysical research communications · 2020
    Article
  11. S-Nitrosylation: An Emerging Paradigm of Redox Signaling.Antioxidants (Basel, Switzerland) · 2019
    Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Xanthine oxidase activity in patients with age-related cataract associated with hypertension.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2018
    Article
  19. Article
  20. Review

15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

C R WhiteDepartment of Medicine, University of Alabama at Birmingham 35294, USA.
V Darley-Usmar
W R Berrington
M McAdams
J Z Gore
J A Thompson
D A Parks
M M Tarpey
B A Freeman
Duke Medical Center · US

Funding

REACTIVE SPECIES IN ATHEROSCLEROSIS--OXIDIZED LDL ROLEK08HL003457 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI TARPEY, MARGARET M · 1996 to 1999
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VASCULAR ENDOTHELIAL OXIDANT METABOLISMP01HL048676 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BECKMAN, JOSEPH S · 1992 to 1998
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LUNG FREE RADICAL METABOLISM AND INJURYR01HL051245 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI FREEMAN, BRUCE A · 1994 to 1998
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NHLBI NIH HHS KO8-HL03457NHLBI NIH HHS P01-HL48676NHLBI NIH HHS R01-HL51245
6 · The paper itself

Abstract

Reactive oxygen species play a central role in vascular inflammation and atherogenesis, with enhanced superoxide (O2.-) production contributing significantly to impairment of nitric oxide (.NO)-dependent relaxation of vessels from cholesterol-fed rabbits. We investigated potential sources of O2.- production, which contribute to this loss of endothelium-dependent vascular responses. The vasorelaxation elicited by acetylcholine (ACh) in phenylephrine-contracted, aortic ring segments was impaired by cholesterol feeding. Pretreatment of aortic vessels with either heparin, which competes with xanthine oxidase (XO) for binding to sulfated glycosaminoglycans, or the XO inhibitor allopurinol resulted in a partial restoration (36-40% at 1 muM ACh) of ACh-dependent relaxation. Furthermore, O2.(-)-dependent lucigenin chemiluminescence, measured in intact ring segments from hypercholesterolemic rabbits, was decreased by addition of heparin, allopurinol or a chimeric, heparin-binding superoxide dismutase. XO activity was elevated more than two-fold in plasma of hypercholesterolemic rabbits. Incubation of vascular rings from rabbits on a normal diet with purified XO (10 milliunits/ml) also impaired .NO-dependent relaxation but only in the presence of purine substrate. As with vessels from hypercholesterolemic rabbits, this effect was prevented by heparin and allopurinol treatment. We hypothesize that increases in plasma cholesterol induce the release of XO into the circulation, where it binds to endothelial cell glycosaminoglycans. Only in hypercholesterolemic vessels is sufficient substrate available to sustain the production of O2.- and impair NO-dependent vasorelaxation. Chronically, the continued production of peroxynitrite, (ONOO-) which the simultaneous generation of NO and O2.- implies, may irreversibly impair vessel function.

Indexed as

AcetylcholineAnimalsEndothelium, VascularGlycosaminoglycansHypercholesterolemiaIn Vitro TechniquesLuminescent MeasurementsMuscle, Smooth, VascularNitric OxideRabbitsSuperoxidesVasodilationXanthine OxidaseAcetylcholineGlycosaminoglycansNitric OxideSuperoxidesXanthine Oxidase

Identifiers

PMID8710942
PMCPMC38744
OpenAlexW2012018808

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.