The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Hypercholesterolemia increases endothelial superoxide anion production.
Open accessAbstract
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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“Its mechanism of action is based on the reaction with the FAD moiety of the NOX dehydrogenase domain (699).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [699]
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Cites
Furchgott, R. F., & Zawadzki, J. V. (1980) · Nature · doi:10.1038/288373a0 · Cited by 12,064
Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704
Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., & Freeman, B. A. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.4.1620 · Cited by 7,029
Babior, B. M., Kipnes, R. S., & Curnutte, J. T. (1973) · Journal of Clinical Investigation · doi:10.1172/jci107236 · Cited by 2,931
Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor
Gryglewski, R. J., Palmer, R. M. J., & Moncada, S. (1986) · Nature · doi:10.1038/320454a0 · Cited by 2,400
Abnormal Endothelium-Dependent Vascular Relaxation in Patients with Essential Hypertension
Panza, J. A., Quyyumi, A. A., Brush, J. E., & Epstein, S. E. (1990) · New England Journal of Medicine · doi:10.1056/nejm199007053230105 · Cited by 2,366
Quantitative Aspects of the Production of Superoxide Anion Radical by Milk Xanthine Oxidase
Fridovich, I. (1970) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)62884-4 · Cited by 1,035
Myers, P. R., Minor, R. L., Guerra, R., Bates, J. N., & Harrison, D. G. (1990) · Nature · doi:10.1038/345161a0 · Cited by 973
Self-citationAllen, R. C., STJERNHOLM, R. L., & Steele, R. H. (1972) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(72)90545-1 · Cited by 955
Endothelium-dependent vasodilation is attenuated in patients with heart failure.
Kubo, S. H., Rector, T. S., Bank, A. J., Williams, R. E., & Heifetz, S. M. (1991) · Circulation · doi:10.1161/01.cir.84.4.1589 · Cited by 775
The Regulation of Rat Liver Xanthine Oxidase
Stirpe, F., Corte, E. D., & Lorenzoni, E. (1969) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36428-1 · Cited by 733
The extinction coefficient of cytochrome c
GELDER, B. F. V., & Slater, E. C. (1962) · Biochimica et Biophysica Acta · doi:10.1016/0006-3002(62)90073-2 · Cited by 700
Fong, K.-L., McCay, P. B., Poyer, J. L., Keele, B. B., & Misra, H. P. (1973) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)43258-4 · Cited by 650
Superoxide radicals as precursors of mitochondrial hydrogen peroxide
Loschen, G., Azzi, A., Richter, C., & Flohé, L. (1974) · FEBS Letters · doi:10.1016/0014-5793(74)80281-4 · Cited by 634
Diet-induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta.
Minor, R. L., Myers, P. R., Guerra, R., Bates, J. N., & Harrison, D. G. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114949 · Cited by 517
Self-citationCorte, E. D., & Stirpe, F. (1972) · Biochemical Journal · doi:10.1042/bj1260739 · Cited by 437
Freiman, P., Mitchell, G. G., Heistad, D. D., Armstrong, M. L., & Harrison, D. G. (1986) · Circulation Research · doi:10.1161/01.res.58.6.783 · Cited by 405
Self-citationDetection of superoxide generated by endothelial cells.
Rosen, G. M., & Freeman, B. Α. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.23.7269 · Cited by 402
Mügge, A., Elwell, J. H., Peterson, T. E., Hofmeyer, T. G., Heistad, D. D., & Harrison, D. G. (1991) · Circulation Research · doi:10.1161/01.res.69.5.1293 · Cited by 399
Self-citationOxygen-derived free radicals, endothelium, and responsiveness of vascular smooth muscle
Rubanyi, G. M., & Vanhoutte, P. M. (1986) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1986.250.5.h815 · Cited by 376
Lucigenin chemiluminescence in the assessment of neutrophil superoxide production
Gyllenhammar, H. (1987) · Journal of Immunological Methods · doi:10.1016/0022-1759(87)90461-3 · Cited by 355
Conversion of xanthine dehydrogenase to oxidase in ischemic rat tissues.
Engerson, T. D., McKelvey, T. G., Rhyne, D. B., Boggio, E. B., Snyder, S. J., & Jones, H. P. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112990 · Cited by 350
Attenuation of endothelium-dependent relaxation in aorta from diabetic rats
Oyama, Y., 川崎, 久., Hattori, Y., & Kanno, M. (1986) · European Journal of Pharmacology · doi:10.1016/0014-2999(86)90013-0 · Cited by 342
Coronary Vascular Reactivity After Acute Myocardial Ischemia
Ku, D. D. (1982) · Science · doi:10.1126/science.7123259 · Cited by 328
Metabolic studies of allopurinol, an inhibitor of xanthine oxidase
Elion, G. B., Kovensky, A., Hitchings, G. H., Metz, E. N., & Rundles, R. W. (1966) · Biochemical Pharmacology · doi:10.1016/0006-2952(66)90163-8 · Cited by 327
Mügge, A., Elwell, J. H., Peterson, T. E., & Harrison, D. G. (1991) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1991.260.2.c219 · Cited by 314
Self-citationKontos, H. A., Wei, E. P., Ellis, E. F., Jenkins, L. W., Povlishock, J. T., Rowe, G. T., & Hess, M. L. (1985) · Circulation Research · doi:10.1161/01.res.57.1.142 · Cited by 291
Ignarro, L. J., Byrns, R. E., Buga, G. M., Wood, K. S., & Chaudhuri, G. (1988) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24231-8 · Cited by 232
Role of superoxide in endothelial-cell modification of low-density lipoproteins
Steinbrecher, U. P. (1988) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(88)90145-2 · Cited by 227
Mediator‐induced activation of xanthine oxidase in endothelial cells
Friedl, H. P., Till, G. O., Ryan, U. S., & Ward, P. A. (1989) · The FASEB Journal · doi:10.1096/fasebj.3.13.2806779 · Cited by 218
Doyle, M. P., Mahapatro, S. N., Broene, R. D., & Guy, J. K. (1988) · Journal of the American Chemical Society · doi:10.1021/ja00210a047 · Cited by 213
Omar, H. Α., Cherry, P., Mortelliti, M. P., Burke-Wolin, T., & Wolin, M. S. (1991) · Circulation Research · doi:10.1161/01.res.69.3.601 · Cited by 212
Matsubara, T., & Ziff, M. (1986) · Journal of Cellular Physiology · doi:10.1002/jcp.1041270203 · Cited by 165
Superoxide anion production by the autoxidation of cytochrome P450cam
Sligar, S. G., Lipscomb, J. D., Debrunner, P. G., & GUNSALUS, I. C. (1974) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(74)90565-8 · Cited by 139
Cholesterol feeding impairs endothelium-dependent relaxation of rabbit aorta
Jayakody, R. L., SENARATNE, M. P. J., Thomson, A. B. R., & Kappagoda, C. T. (1985) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y85-199 · Cited by 119
Superoxide anion inhibits cGMP-associated bovine pulmonary arterial relaxation
Cherry, P. D., Omar, H. Α., Farrell, K. A., Stuart, J. S., & Wolin, M. S. (1990) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1990.259.4.h1056 · Cited by 112
Lamping, K. G., & Dole, W. P. (1987) · Circulation Research · doi:10.1161/01.res.61.6.904 · Cited by 84
Superoxide generation by human monocytes and macrophages
Weiss, S. J., King, G. W., & LoBuglio, A. F. (1978) · American Journal of Hematology · doi:10.1002/ajh.2830040102 · Cited by 39
Alkaline Bohr effect of human hemoglobin Ao
Di, E., Doyle, M. L., & Gill, S. J. (1988) · Journal of Molecular Biology · doi:10.1016/0022-2836(88)90545-1 · Cited by 25
Nitroblue Tetrazolium Reduction in Lymphocytes
Melinn, M., & McLaughlin, H. (1987) · Journal of Leukocyte Biology · doi:10.1002/jlb.41.4.325 · Cited by 22
Heim, K. F., Thomas, G. R., & Ramwell, P. W. (1990) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)23050-6 · Cited by 20
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Dröge, W. (2002) · Physiological Reviews · doi:10.1152/physrev.00018.2001 · Cited by 9,855
Increased oxidative stress in obesity and its impact on metabolic syndrome
Furukawa, S., Fujita, T., Shimabukuro, M., Iwaki, M., Yamada, Y., Nakajima, Y., Nakayama, O., Makishima, M., Matsuda, M., & Shimomura, I. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21625 · Cited by 5,508
Corretti, M. C., Anderson, T. J., Benjamin, E. J., Celermajer, D. S., Charbonneau, F., Creager, M. A., Deanfield, J. E., Drexler, H., Gerhard‐Herman, M. D., Herrington, D. M., et al. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(01)01746-6 · Cited by 4,606
Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress
Cai, H., & Harrison, D. G. (2000) · Circulation Research · doi:10.1161/01.res.87.10.840 · Cited by 3,839
Self-citationNAD(P)H Oxidase: Role in Cardiovascular Biology and Disease
Griendling, K. K., Sorescu, D., & Ushio-Fukai, M. (2000) · Circulation Research · doi:10.1161/01.res.86.5.494 · Cited by 2,886
Metadata
- Authors
- Ohara, Y., Peterson, T. E., & Harrison, D. G.
- Affiliations
- Emory University (US)
- ORCID
- Harrison, D G
- Venue
- Journal of Clinical Investigation
- Published
- 1993-06-01
- Volume
- 91
- Issue
- 6
- Pages
- 2546-2551
- ISSN
- 0021-9738 (ISSN-L)
- 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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