Table of Contents
Cardiovascular Psychiatry and Neurology
Volume 2009, Article ID 282059, 9 pages
http://dx.doi.org/10.1155/2009/282059
Review Article

The Potential for Xanthine Oxidase Inhibition in the Prevention and Treatment of Cardiovascular and Cerebrovascular Disease

Division of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow G11 6NT, UK

Received 2 June 2009; Accepted 8 September 2009

Academic Editor: Milos Ikonomovic

Copyright © 2009 Peter Higgins et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. George and A. D. Struthers, “The role of urate and xanthine oxidase inhibitors in cardiovascular disease,” Cardiovascular Therapeutics, vol. 26, no. 1, pp. 59–64, 2008. View at Publisher · View at Google Scholar · View at PubMed
  2. C. E. Berry and J. M. Hare, “Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications,” Journal of Physiology, vol. 555, no. 3, pp. 589–606, 2004. View at Publisher · View at Google Scholar · View at PubMed
  3. Z. Zhang, D. R. Blake, C. R. Stevens et al., “A reappraisal of xanthine dehydrogenase and oxidase in hypoxic reperfusion injury: the role of NADH as an electron donor,” Free Radical Research, vol. 28, no. 2, pp. 151–164, 1998. View at Google Scholar
  4. R. Hille and V. Massey, “Studies on the oxidative half-reaction of xanthine oxidase,” The Journal of Biological Chemistry, vol. 256, no. 17, pp. 9090–9095, 1981. View at Google Scholar
  5. C. J. Weir, S. W. Muir, M. R. Walters, and K. R. Lees, “Serum urate as an independent predictor of poor outcome and future vascular events after acute stroke,” Stroke, vol. 34, no. 8, pp. 1951–1956, 2003. View at Publisher · View at Google Scholar · View at PubMed
  6. A. Cherubini, M. C. Polidori, M. Bregnocchi et al., “Antioxidant profile and early outcome in stroke patients,” Stroke, vol. 31, no. 10, pp. 2295–2300, 2000. View at Google Scholar
  7. J. Dawson, K. R. Lees, C. J. Weir et al., “Baseline serum urate and 90-day functional outcomes following acute ischemic stroke,” Cerebrovascular Diseases, vol. 28, no. 2, pp. 202–203, 2009. View at Publisher · View at Google Scholar · View at PubMed
  8. A. Chamorro, V. Obach, A. Cervera, M. Revilla, R. Deulofeu, and J. H. Aponte, “Prognostic significance of uric acid serum concentration in patients with acute ischemic stroke,” Stroke, vol. 33, no. 4, pp. 1048–1052, 2002. View at Publisher · View at Google Scholar
  9. S. Lehto, L. Niskanen, T. Ronnemaa, and M. Laakso, “Serum uric acid is a strong predictor of stroke in patients with non-insulin-dependent diabetes mellitus,” Stroke, vol. 29, no. 3, pp. 635–639, 1998. View at Google Scholar
  10. E. J. Newman, F. S. Rahman, K. R. Lees, C. J. Weir, and M. R. Walters, “Elevated serum urate concentration independently predicts poor outcome following stroke in patients with diabetes,” Diabetes-Metabolism Research and Reviews, vol. 22, no. 1, pp. 79–82, 2006. View at Publisher · View at Google Scholar · View at PubMed
  11. T. E. Madsen, J. B. Muhlestein, J. F. Carlquist et al., “Serum uric acid independently predicts mortality in patients with significant, angiographically defined coronary disease,” American Journal of Nephrology, vol. 25, no. 1, pp. 45–49, 2005. View at Publisher · View at Google Scholar · View at PubMed
  12. C. Bickel, H. J. Rupprecht, S. Blankenberg et al., “Serum uric acid as an independent predictor of mortality in patients with angiographically proven coronary artery disease,” American Journal of Cardiology, vol. 89, no. 1, pp. 12–17, 2002. View at Publisher · View at Google Scholar
  13. L. V. Franse, M. Pahor, M. D. Bari et al., “Serum uric acid, diuretic treatment and risk of cardiovascular events in the systolic hypertension in the elderly program (SHEP),” Journal of Hypertension, vol. 18, no. 8, pp. 1149–1154, 2000. View at Google Scholar
  14. M. H. Alderman, H. Cohen, S. Madhavan, and S. Kivlighn, “Serum uric acid and cardiovascular events in successfully treated hypertensive patients,” Hypertension, vol. 34, no. 1, pp. 144–150, 1999. View at Google Scholar
  15. J.-G. Wang, J. A. Staessen, R. H. Fagard, W. H. Birkenhager, L. Gong, and L. Liu, “Prognostic significance of serum creatinine and uric acid in older Chinese patients with isolated systolic hypertension,” Hypertension, vol. 37, no. 4, pp. 1069–1074, 2001. View at Google Scholar
  16. P. Verdecchia, G. Schillaci, G. Reboldi, F. Santeusanio, C. Porcellati, and P. Brunetti, “Relation between serum uric acid and risk of cardiovascular disease in essential hypertension: the PIUMA study,” Hypertension, vol. 36, no. 6, pp. 1072–1078, 2000. View at Google Scholar
  17. P. W. de Leeuw, L. Thijs, W. H. Birkenhager et al., “Systolic hypertension in Europe (Syst-Eur) trial investigators. Prognostic significance of renal function in elderly patients with isolated systolic hypertension: results from the Syst-Eur trial,” Journal of the American Society of Nephrology, vol. 13, pp. 2213–2222, 2002. View at Google Scholar
  18. J.-H. Chen, S.-Y. Chuang, H.-J. Chen, W. T. Yeh, and W. H. Pan, “Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a chinese cohort study,” Arthritis Care & Research, vol. 61, no. 2, pp. 225–232, 2009. View at Publisher · View at Google Scholar · View at PubMed
  19. A. M. Strasak, C. C. Kelleher, L. J. Brant et al., “Serum uric acid is an independent predictor for all major forms of cardiovascular death in 28,613 elderly women: a prospective 21-year follow-up study,” International Journal of Cardiology, vol. 125, no. 2, pp. 232–239, 2008. View at Publisher · View at Google Scholar · View at PubMed
  20. D. J. Schretlen, A. B. Inscore, T. D. Vannorsdall et al., “Serum uric acid and brain ischemia in normal elderly adults,” Neurology, vol. 69, no. 14, pp. 1418–1423, 2007. View at Publisher · View at Google Scholar · View at PubMed
  21. A. Enomoto, H. Kimura, A. Chairoungdua et al., “Molecular identification of a renal urate-anion exchanger that regulates blood urate levels,” Nature, vol. 417, no. 6887, pp. 447–452, 2002. View at Publisher · View at Google Scholar · View at PubMed
  22. C. J. Eastmond, M. Carton, S. Robins, and S. Riddoch, “The effects of alcoholic beverages on urate metabolism in gout sufferers,” British Journal of Rheumatology, vol. 34, no. 8, pp. 756–759, 1995. View at Google Scholar
  23. M. J. MacLachlan and G. P. Rodnan, “Effects of food fast and alcohol on serum uric acid levels and occurrence of acute attacks of gout,” Arthritis & Rheumatism, vol. 8, p. 454, 1965. View at Google Scholar
  24. B. N. Ames, R. Cathcart, E. Schwiers, and P. Hochstein, “Uric-acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 78, no. 11, pp. 6858–6862, 1981. View at Google Scholar
  25. J. Dawson and M. Walters, “Uric acid and xanthine oxidase: future therapeutic targets in the prevention of cardiovascular disease?” British Journal of Clinical Pharmacology, vol. 62, no. 6, pp. 633–644, 2006. View at Publisher · View at Google Scholar · View at PubMed
  26. J. Fang and M. H. Alderman, “Serum uric acid and cardiovascular mortality: the NHANES I epidemiologic follow-up study, 1971–1992,” Journal of the American Medical Association, vol. 283, no. 18, pp. 2404–2410, 2000. View at Google Scholar
  27. M. J. Bos, P. J. Koudstaal, A. Hofman, J. C. M. Witteman, and M. M. B. Breteler, “Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam study,” Stroke, vol. 37, no. 6, pp. 1503–1507, 2006. View at Publisher · View at Google Scholar · View at PubMed
  28. J. Dawson, Y. Nalci, G. T. McInnes et al., “Serum uric acid and stroke mortality in patients with hypertension,” Journal of Human Hypertension, vol. 21, pp. 843–844, 2007. View at Google Scholar
  29. A. Karagiannis, D. P. Mikhailidis, K. Tziomalos et al., “Serum uric acid as an independent predictor of early death after acute stroke,” Circulation Journal, vol. 71, no. 7, pp. 1120–1127, 2007. View at Publisher · View at Google Scholar
  30. I. K. de Scheerder, A. M. M. van de Kraay, J. M. J. Lamers, J. F. Koster, J. W. de Jong, and P. W. Serruys, “Myocardial malonidialdehyde and uric acid release after short-lasting coronary occlusions during coronary angioplasty: potential mechanisms for free radical generation,” American Journal of Cardiology, vol. 68, no. 4, pp. 392–395, 1991. View at Publisher · View at Google Scholar
  31. M. H. Ginsberg, F. Kozin, M. O'Malley, and D. J. McCarty, “Release of platelet constituents by monosodium urate crystals,” The Journal of Clinical Investigation, vol. 60, no. 5, pp. 999–1007, 1977. View at Google Scholar
  32. G. N. Rao, M. A. Corson, and B. C. Berk, “Uric acid stimulates vascular smooth muscle cell proliferation by increasing platelet-derived growth factor A-chain expression,” The Journal of Biological Chemistry, vol. 266, no. 13, pp. 8604–8608, 1991. View at Google Scholar
  33. M. Mazzali, J. Kanellis, L. Han et al., “Hyperuricemia induces a primary renal arteriolapathy in rats by a blood pressure-independent mechanism,” American Journal of Physiology, vol. 282, pp. F991–F997, 2002. View at Google Scholar
  34. I. Saito, T. Saruta, K. Kondo et al., “Serum uric acid and the renin-angiotensin system in hypertension,” Journal of the American Geriatrics Society, vol. 26, no. 6, pp. 241–247, 1978. View at Google Scholar
  35. A. R. Dyer, K. Liu, M. Walsh, C. Kiefe, D. R. Jacobs Jr., and D. E. Bild, “Ten-year incidence of elevated blood pressure and its predictors: the CARDIA Study,” Journal of Human Hypertension, vol. 13, no. 1, pp. 13–21, 1999. View at Google Scholar
  36. W. S. Waring, D. J. Webb, and S. R. J. Maxwell, “Systemic uric acid administration increases serum antioxidant capacity in healthy volunteers,” Journal of Cardiovascular Pharmacology, vol. 38, no. 3, pp. 365–371, 2001. View at Publisher · View at Google Scholar
  37. F. J. Nieto, C. Iribarren, M. D. Gross, G. W. Comstock, and R. G. Cutler, “Uric acid and serum antioxidant capacity: a reaction to atherosclerosis?” Atherosclerosis, vol. 148, no. 1, pp. 131–139, 2000. View at Publisher · View at Google Scholar
  38. W. S. Waring, “Uric acid: an important antioxidant in acute ischaemic stroke,” QJM, vol. 95, no. 10, pp. 691–693, 2002. View at Google Scholar
  39. H. Kanemitsu, A. Tamura, T. Kirino et al., “Xanthine and uric acid levels in rat brain following focal ischemia,” Journal of Neurochemistry, vol. 51, no. 6, pp. 1882–1885, 1988. View at Google Scholar
  40. Z. F. Yu, A. J. Bruce-Keller, Y. Goodman, and M. P. Mattson, “Uric acid protects neurons against excitotoxic and metabolic insults in cell culture, and against focal ischemic brain injury in vivo,” Journal of Neuroscience Research, vol. 53, no. 5, pp. 613–625, 1998. View at Publisher · View at Google Scholar
  41. G. L. Squadrito, R. Cueto, A. E. Splenser et al., “Reaction of uric acid with peroxynitrite and implications for the mechanism of neuroprotection by uric acid,” Archives of Biochemistry & Biophysics, vol. 376, no. 2, pp. 333–337, 2000. View at Publisher · View at Google Scholar · View at PubMed
  42. E. C. Tayag, S. N. Nair, S. Wahhab, C. D. Katsetos, J. W. Lighthall, and J. C. Lehmann, “Cerebral uric acid increases following experimental traumatic brain injury in rat,” Brain Research, vol. 733, no. 2, pp. 287–291, 1996. View at Publisher · View at Google Scholar
  43. S. Spitsin, D. C. Hooper, T. Mikheeva, and H. Koprowski, “Uric acid levels in patients with multiple sclerosis: analysis in mono- and dizygotic twins,” Multiple Sclerosis, vol. 7, no. 3, pp. 165–166, 2001. View at Publisher · View at Google Scholar
  44. S. Amaro, D. Soy, V. Obach, Á. Cervera, A. M. Planas, and Á. Chamorro, “A pilot study of dual treatment with recombinant tissue plasminogen activator and uric acid in acute ischemic stroke,” Stroke, vol. 38, no. 7, pp. 2173–2175, 2007. View at Publisher · View at Google Scholar · View at PubMed
  45. H. K. Choi and E. S. Ford, “Haemoglobin A1c, fasting glucose, serum C-peptide and insulin resistance in relation to serum uric acid levels—the Third National Health and Nutrition Examination Survey,” Rheumatology, vol. 47, no. 5, pp. 713–717, 2008. View at Publisher · View at Google Scholar · View at PubMed
  46. D. Conen, V. Wietlisbach, P. Bovet et al., “Prevalence of hyperuricemia and relation of serum uric acid with cardiovascular risk factors in a developing country,” BMC Public Health, vol. 4, pp. 1–9, 2004. View at Publisher · View at Google Scholar · View at PubMed
  47. E. S. Ford, C. Y. Li, S. Cook, and H. K. Choi, “Serum concentrations of uric acid and the metabolic syndrome among US children and adolescents,” Circulation, vol. 115, no. 19, pp. 2526–2532, 2007. View at Publisher · View at Google Scholar · View at PubMed
  48. D. I. Feig, T. Nakagawa, S. A. Karumanchi et al., “Hypothesis: uric acid, nephron number, and the pathogenesis of essential hypertension,” Kidney International, vol. 66, no. 1, pp. 281–287, 2004. View at Publisher · View at Google Scholar · View at PubMed
  49. D. I. Feig, “Uric acid and hypertension in adolescents,” Seminars in Nephrology, vol. 25, no. 1, pp. 32–38, 2005. View at Publisher · View at Google Scholar
  50. C. Berry, C. A. Hamilton, M. J. Brosnan et al., “Investigation into the sources of superoxide in human blood vessels: angiotensin II increases superoxide production in human internal mammary arteries,” Circulation, vol. 101, no. 18, pp. 2206–2212, 2000. View at Google Scholar
  51. Y. Hellsten-Westing, “Immunohistochemical localization of xanthine oxidase in human cardiac and skeletal muscle,” Histochemistry, vol. 100, no. 3, pp. 215–222, 1993. View at Google Scholar
  52. D. Harrison, K. K. Griendling, U. Landmesser, B. Hornig, and H. Drexler, “Role of oxidative stress in atherosclerosis,” American Journal of Cardiology, vol. 91, supplement 3, pp. 7A–11A, 2003. View at Publisher · View at Google Scholar
  53. N. R. Madamanchi, A. Vendrov, and M. S. Runge, “Oxidative stress and vascular disease,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 1, pp. 29–38, 2005. View at Publisher · View at Google Scholar · View at PubMed
  54. C. A. Hamilton, W. H. Miller, S. Al-Benna et al., “Strategies to reduce oxidative stress in cardiovascular disease,” Clinical Science, vol. 106, no. 3, pp. 219–234, 2004. View at Publisher · View at Google Scholar · View at PubMed
  55. T. M. Paravicini, G. R. Drummond, and C. G. Sobey, “Reactive oxygen species in the cerebral circulation: physiological roles and therapeutic implications for hypertension and stroke,” Drugs, vol. 64, no. 19, pp. 2143–2157, 2004. View at Publisher · View at Google Scholar
  56. G. M. Keating and D. Ormrod, “Micronised fenofibrate: an updated review of its clinical efficacy in the management of dyslipidaemia,” Drugs, vol. 62, no. 13, pp. 1909–1944, 2002. View at Google Scholar
  57. J. P. Desager, R. Hulhoven, and C. Harvengt, “Uricosuric effect of fenofibrate in healthy volunteers,” Journal of Clinical Pharmacology, vol. 20, no. 10, pp. 560–564, 1980. View at Google Scholar
  58. M. Elisaf, V. Tsimichodimos, E. Bairaktari, and K. C. Siamopoulos, “Effect of micronized fenofibrate and losartan combination on uric acid metabolism in hypertensive patients with hyperuricemia,” Journal of Cardiovascular Pharmacology, vol. 34, no. 1, pp. 60–63, 1999. View at Publisher · View at Google Scholar
  59. M. D. Bastow, P. N. Durrington, and M. Ishola, “Hypertriglyceridemia and hyperuricemia: effects of two fibric acid derivatives (bezafibrate and fenofibrate) in a double-blind, placebo-controlled trial,” Metabolism, vol. 37, no. 3, pp. 217–220, 1988. View at Google Scholar
  60. M. Burnier, B. Waeber, and H. R. Brunner, “Clinical pharmacology of the angiotensin II receptor antagonist losartan potassium in healthy subjects,” Journal of Hypertension, vol. 13, no. 1, pp. S23–S28, 1995. View at Google Scholar
  61. M. Burnier, F. Roch-Ramel, and H. R. Brunner, “Renal effects of angiotensin II receptor blockade in normotensive subjects,” Kidney International, vol. 49, no. 6, pp. 1787–1790, 1996. View at Google Scholar
  62. B. Dahlöf, R. B. Devereux, S. E. Kjeldsen et al., “Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol,” The Lancet, vol. 359, no. 9311, pp. 995–1003, 2002. View at Publisher · View at Google Scholar · View at PubMed
  63. A. Høieggen, M. H. Alderman, S. E. Kjeldsen et al., “The impact of serum uric acid on cardiovascular outcomes in the LIFE study,” Kidney International, vol. 65, no. 3, pp. 1041–1049, 2004. View at Publisher · View at Google Scholar · View at PubMed
  64. V. G. Athyros, M. Elisaf, A. A. Papageorgiou et al., “Effect of statins versus untreated dyslipidemia on serum uric acid levels in patients with coronary heart disease: a subgroup analysis of the GREek atorvastatin and coronary-heart-disease evaluation (GREACE) study,” American Journal of Kidney Diseases, vol. 43, no. 4, pp. 589–599, 2004. View at Publisher · View at Google Scholar
  65. J. George, E. Carr, J. Davies, J. F. Belch, and A. Struthers, “High-dose allopurinol improves endothelial function by profoundly reducing vascular oxidative stress and not by lowering uric acid,” Circulation, vol. 114, no. 23, pp. 2508–2516, 2006. View at Publisher · View at Google Scholar · View at PubMed
  66. G. B. Elion, “Enzymatic and metabolic studies with allopurinol,” Annals of the Rheumatic Diseases, vol. 25, no. 6, pp. 608–614, 1966. View at Google Scholar
  67. T. P. Cappola, D. A. Kass, G. S. Nelson et al., “Allopurinol improves myocardial efficiency in patients with idiopathic dilated cardiomyopathy,” Circulation, vol. 104, no. 20, pp. 2407–2411, 2001. View at Google Scholar
  68. A. M. Shehab, R. Butler, R. J. MacFadyen, and A. D. Struthers, “A placebo-controlled study examining the effect of allopurinol on heart rate variability and dysrhythmia counts in chronic heart failure,” British Journal of Clinical Pharmacology, vol. 51, no. 4, pp. 329–334, 2001. View at Publisher · View at Google Scholar
  69. W. Doehner, N. Schoene, M. Rauchhaus et al., “Effects of xanthine oxidase inhibition with allopurinol on endothelial function and peripheral blood flow in hyperuricemic patients with chronic heart failure: results from 2 placebo-controlled studies,” Circulation, vol. 105, no. 22, pp. 2619–2624, 2002. View at Publisher · View at Google Scholar
  70. C. A. Farquharson, R. Butler, A. Hill, J. F. Belch, and A. D. Struthers, “Allopurinol improves endothelial dysfunction in chronic heart failure,” Circulation, vol. 106, no. 2, pp. 221–226, 2002. View at Publisher · View at Google Scholar
  71. A. D. Gavin and A. D. Struthers, “Allopurinol reduces B-type natriuretic peptide concentrations and haemoglobin but does not alter exercise capacity in chronic heart failure,” Heart, vol. 91, no. 6, pp. 749–753, 2005. View at Publisher · View at Google Scholar · View at PubMed
  72. H. E. Cingolani, J. A. Plastino, E. M. Escudero, B. Mangal, J. Brown, and N. G. Perez, “The effect of xanthine oxidase inhibition upon ejection fraction in heart failure patients: La Plata Study,” Journal of Cardiac Failure, vol. 12, no. 7, pp. 491–498, 2006. View at Publisher · View at Google Scholar · View at PubMed
  73. J. M. Hare, B. Mangal, J. Brown et al., “Impact of oxypurinol in patients with symptomatic heart failure. results of the OPT-CHF study,” Journal of the American College of Cardiology, vol. 51, no. 24, pp. 2301–2309, 2008. View at Publisher · View at Google Scholar · View at PubMed
  74. The EXOTIC-EF Study, Cardiome Press Releases, 2008.
  75. S. Baldus, R. Koster, P. Chumley et al., “Oxypurinol improves coronary and peripheral endothelial function in patients with coronary artery disease,” Free Radical Biology & Medicine, vol. 39, no. 9, pp. 1184–1190, 2005. View at Publisher · View at Google Scholar · View at PubMed
  76. S. Baldus, K. Müllerleile, P. Chumley et al., “Inhibition of xanthine oxidase improves myocardial contractility in patients with ischemic cardiomyopathy,” Free Radical Biology & Medicine, vol. 41, no. 8, pp. 1282–1288, 2006. View at Publisher · View at Google Scholar · View at PubMed
  77. S. W. Muir, C. Harrow, J. Dawson et al., “Allopurinol use yields potentially beneficial effects on inflammatory indices in those with recent ischemic stroke: a randomized, double-blind, placebo-controlled trial,” Stroke, vol. 39, no. 12, pp. 3303–3307, 2008. View at Publisher · View at Google Scholar · View at PubMed
  78. R. Butler, A. D. Morris, J. F. Belch, A. Hill, and A. D. Struthers, “Allopurinol normalizes endothelial dysfunction in type 2 diabetics with mild hypertension,” Hypertension, vol. 35, no. 3, pp. 746–751, 2000. View at Google Scholar
  79. M.-C. Desco, M. Asensi, R. Márquez et al., “Xanthine oxidase is involved in free radical production in type 1 diabetes: protection by allopurinol,” Diabetes, vol. 51, no. 4, pp. 1118–1124, 2002. View at Google Scholar
  80. M. Afshari, B. Larijani, A. Rezaie et al., “Ineffectiveness of allopurinol in reduction of oxidative stress in diabetic patients; a randomized, double-blind placebo-controlled clinical trial,” Biomedicine & Pharmacotherapy, vol. 58, no. 10, pp. 546–550, 2004. View at Publisher · View at Google Scholar · View at PubMed
  81. C. Cardillo, C. M. Kilcoyne, R. O. Cannon III, A. A. Quyyumi, and J. A. Panza, “Xanthine oxidase inhibition with oxypurinol improves endothelial vasodilator function in hypercholesterolemic but not in hypertensive patients,” Hypertension, vol. 30, no. 1, pp. 57–63, 1997. View at Google Scholar
  82. J. G. O'Driscoll, D. J. Green, J. M. Rankin, and R. R. Taylor, “Nitric oxide-dependent endothelial function is unaffected by allopurinol in hypercholesterolaemic subjects,” Clinical & Experimental Pharmacology & Physiology, vol. 26, no. 10, pp. 779–783, 1999. View at Publisher · View at Google Scholar
  83. S. Guthikonda, C. Sinkey, T. Barenz, and W. G. Haynes, “Xanthine oxidase inhibition reverses endothelial dysfunction in heavy smokers,” Circulation, vol. 107, no. 3, pp. 416–421, 2003. View at Publisher · View at Google Scholar
  84. G. Mercuro, C. Vitale, E. Cerquetani et al., “Effect of hyperuricemia upon endothelial function in patients at increased cardiovascular risk,” American Journal of Cardiology, vol. 94, no. 7, pp. 932–935, 2004. View at Publisher · View at Google Scholar · View at PubMed
  85. O. Yiginer, F. Ozcelik, T. Inanc et al., “Allopurinol improves endothelial function and reduces oxidant-inflammatory enzyme of myeloperoxidase in metabolic syndrome,” Clinical Research in Cardiology, vol. 97, no. 5, pp. 334–340, 2008. View at Publisher · View at Google Scholar · View at PubMed
  86. A. A. El Solh, R. Saliba, T. Bosinski, B. J. Grant, E. Berbary, and N. Miller, “Allopurinol improves endothelial function in sleep apnoea: a randomised controlled study,” European Respiratory Journal, vol. 27, no. 5, pp. 997–1002, 2006. View at Publisher · View at Google Scholar · View at PubMed
  87. F. Khan, J. George, K. Wong, S. McSwiggan, A. D. Struthers, and J. F. Belch, “Allopurinol treatment reduces arterial wave reflection in stroke survivors,” Cardiovascular Therapeutics, vol. 26, no. 4, pp. 247–252, 2008. View at Publisher · View at Google Scholar · View at PubMed
  88. W. Guan, T. Osanai, T. Kamada et al., “Effect of allopurinol pretreatment on free radical generation after primary coronary angioplasty for acute myocardial infarction,” Journal of Cardiovascular Pharmacology, vol. 41, no. 5, pp. 699–705, 2003. View at Publisher · View at Google Scholar
  89. L. F. Parmley, A. G. Mufti, and J. M. Downey, “Allupurinol therapy of ischemic heart disease with infarct extension,” Canadian Journal of Cardiology, vol. 8, no. 3, pp. 280–286, 1992. View at Google Scholar
  90. U. Landmesser, S. Spiekermann, C. Preuss et al., “Angiotensin II induces endothelial xanthine oxidase activation: role for endothelial dysfunction in patients with coronary disease,” Arteriosclerosis, Thrombosis, & Vascular Biology, vol. 27, no. 4, pp. 943–948, 2007. View at Publisher · View at Google Scholar · View at PubMed
  91. I. E. Kalyakin and A. F. Mit'kin, “Effects of allopurinol on uric acid metabolism and lipid peroxidation in IHD patients with stable angina pectoris,” Kardiologiya, vol. 33, no. 2, pp. 15–17, 1993. View at Google Scholar
  92. J. B. Rosenfeld, “Effect of long-term allopurinol administration on serial GFR in normotensive and hypertensive hyperuricemic subjects,” Advances in Experimental Medicine & Biology, vol. 41, pp. 581–596, 1974. View at Google Scholar
  93. D. I. Feig, B. Soletsky, and R. J. Johnson, “Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial,” Journal of the American Medical Association, vol. 300, no. 8, pp. 924–932, 2008. View at Publisher · View at Google Scholar · View at PubMed
  94. M. Kanbay, A. Ozkara, Y. Selcoki et al., “Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearence, and proteinuria in patients with normal renal functions,” International Urology & Nephrology, vol. 39, no. 4, pp. 1227–1233, 2007. View at Publisher · View at Google Scholar · View at PubMed
  95. S. Guthikonda, K. Woods, C. A. Sinkey, and W. G. Haynes, “Role of xanthine oxidase in conduit artery endothelial dysfunction in cigarette smokers,” American Journal of Cardiology, vol. 93, no. 5, pp. 664–668, 2004. View at Publisher · View at Google Scholar · View at PubMed
  96. I. Eskurza, Z. D. Kahn, and D. R. Seals, “Xanthine oxidase does not contribute to impaired peripheral conduit artery endothelium-dependent dilatation with ageing,” Journal of Physiology, vol. 571, no. 3, pp. 661–668, 2006. View at Publisher · View at Google Scholar · View at PubMed
  97. L. M. Heunks, J. Viña, C. L. van Herwaarden, H. T. Folgering, A. Gimeno, and P. N. Dekhuijzen, “Xanthine oxidase is involved in exercise-induced oxidative stress in chronic obstructive pulmonary disease,” American Journal of Physiology, vol. 277, no. 6, pp. R1697–R1704, 1999. View at Google Scholar
  98. D. Delample, F. Durand, A. Severac et al., “Implication of xanthine oxidase in muscle oxidative stress in COPD patients,” Free Radical Research, vol. 42, no. 9, pp. 807–814, 2008. View at Publisher · View at Google Scholar · View at PubMed
  99. L. Spahr, S. Bresson-Hadni, P. Amann et al., “Allopurinol, oxidative stress and intestinal permeability in patients with cirrhosis: an open-label pilot study,” Liver International, vol. 27, no. 1, pp. 54–60, 2007. View at Publisher · View at Google Scholar · View at PubMed
  100. A. D. Struthers, P. T. Donnan, P. Lindsay, D. McNaughton, J. Broomhall, and T. M. MacDonald, “Effect of allopurinol on mortality and hospitalisations in chronic heart failure: a retrospective cohort study,” Heart, vol. 87, no. 3, pp. 229–234, 2002. View at Google Scholar
  101. J. Dawson, T. Quinn, C. Harrow et al., “Allopurinol and nitric oxide activity in the cerebral circulation of those with diabetes,” Diabetes Care, vol. 32, no. 1, pp. 135–137, 2009. View at Publisher · View at Google Scholar · View at PubMed