The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Circulating plasma xanthine oxidase contributes to vascular dysfunction in hypercholesterolemic rabbits.
Open accessAbstract
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In addition, BH4 plays a critical role in the catalytic cycle of NOS (87, 204, 377, 904, 933, 1000, 1007).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [1007]
In the citing paper
“Thus, not only is the NO synthesis completely abolished but the protein also becomes an oxidase, generating superoxide instead of NO (191, 972, 1007) (Table 6).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [1007]
In the citing paper
“Mechanistically, when NOS binds BH2 instead of BH4, the ferrous/oxy heme cannot hydroxylate l-arginine to NG-hydroxy-l-arginine, NO synthesis is blocked, and the oxygen is eventually oxidized to superoxide.”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [1007]
Citations
Cites
PROTEOGLYCANS: STRUCTURES AND INTERACTIONS
Kjellén, L., & Lindahl, U. (1991) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.60.070191.002303 · Cited by 1,900
Hypercholesterolemia increases endothelial superoxide anion production.
Ohara, Y., Peterson, T. E., & Harrison, D. G. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116491 · Cited by 1,765
Proteoglycans: Structures And Interactions
Kjellén, L. (1991) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.60.1.443 · Cited by 1,602
Extensive Nitration of Protein Tyrosines in Human Atherosclerosis Detected by Immunohistochemistry
Beckman, J. S., Ye, Y. Z., Anderson, P. G., Chen, J., Accavitti, M. A., Tarpey, M. M., & White, C. R. (1994) · Biological Chemistry Hoppe-Seyler · doi:10.1515/bchm3.1994.375.2.81 · Cited by 1,122
Self-citationDoes superoxide underlie the pathogenesis of hypertension?
Nakazono, K., Watanabe, N., Matsuno, K., Sasaki, J., Sato, T., & Inoue, M. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.22.10045 · Cited by 746
Superoxide and peroxynitrite inatherosclerosis.
White, C. R., Brock, T. A., Chang, L. Y., Crapo, J. D., BRISCOE, P. M., Ku, D. D., Bradley, W. A., Gianturco, S. H., Gore, J. Z., & Freeman, B. Α. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.3.1044 · Cited by 684
Self-citationMünzel, T. F., Sayegh, H. S., Freeman, B. Α., Tarpey, M. M., & Harrison, D. G. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117637 · Cited by 652
Self-citationNitric oxide and oxygen radicals: a question of balance
Darley-Usmar, V. M., Wiseman, H., & Halliwell, B. B. (1995) · FEBS Letters · doi:10.1016/0014-5793(95)00764-z · Cited by 557
Self-citationBossaller, C., Habib, G. B., Yamamoto, H., Williams, C., Wells, S., & Henry, P. D. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112779 · Cited by 531
Pritchard, K. A., Groszek, L., Smalley, D. M., Sessa, W. C., Wu, M., Villalon, P., Wolin, M. S., & Stemerman, M. B. (1995) · Circulation Research · doi:10.1161/01.res.77.3.510 · Cited by 470
Cited by
Sorted by citations
Role of Oxidative Modifications in Atherosclerosis
Stocker, R., & Keaney, J. F. (2004) · Physiological Reviews · doi:10.1152/physrev.00047.2003 · Cited by 2,651
Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis
Förstermann, U., Xia, N., & Li, H. (2017) · Circulation Research · doi:10.1161/circresaha.116.309326 · Cited by 1,519
The Vascular Endothelium and Human Diseases
Rajendran, P., Rengarajan, T., Thangavel, J., Nishigaki, Y., Sakthisekaran, D., Sethi, G., & Nishigaki, I. (2013) · International Journal of Biological Sciences · doi:10.7150/ijbs.7502 · Cited by 1,550
Role of oxidative stress in atherosclerosis
Harrison, D., Griendling, K. K., Landmesser, U., Hornig, B., & Drexler, H. (2003) · The American Journal of Cardiology · doi:10.1016/s0002-9149(02)03144-2 · Cited by 1,275
Pacher, P., Nivorozhkin, A., & Szabó, C. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.1.6 · Cited by 1,218
Metadata
- Authors
- White, C. R., Darley-Usmar, V, Berrington, W. R., McAdams, M., Gore, J. Z., Thompson, J. A., Parks, D. A., Tarpey, M. M., & Freeman, B. A.
- Affiliations
- University of Alabama at Birmingham (US)
- Department of Medicine, University of Alabama at Birmingham 35294, USA.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1996-08-06
- Volume
- 93
- Issue
- 16
- Pages
- 8745-8749
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC38744
- OpenAlex
- W2012018808
- Cited by
- 367
- References
- 39
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 12 · 2017: 12 · 2016: 9 · 2015: 10 · 2014: 17 · 2013: 7 · 2012: 5
- FWCI
- 9.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health (5k08hl003457-04, 5p01hl048676-05, 5r01hl051245-05)
- National Heart, Lung, and Blood Institute (P01 HL 48676, R01 HL 51245, KO8-HL03457)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- xanthine oxidase, hypercholesterolemia, reactive oxygen species, superoxide, endothelial dysfunction, allopurinol, heparin, glycosaminoglycans, peroxynitrite, atherosclerosis, acetylcholine, cholesterol-fed rabbits
- MeSH terms
- Acetylcholine, Animals, Endothelium, Vascular, Glycosaminoglycans, Hypercholesterolemia, Luminescent Measurements, Muscle, Smooth, Vascular, Nitric Oxide, Rabbits, Superoxides, Vasodilation, Xanthine Oxidase, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
