on June 17, 2002
Circulation. 2002
Published online before print June 17, 2002, doi: 10.1161/01.CIR.0000022140.61460.1D
Published online before print June 17, 2002, doi: 10.1161/01.CIR.0000022140.61460.1D
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 8, 2002
From the Department of Clinical Pharmacology and Therapeutics (C.A.J.F., R.B., A.D.S.) and the Department of Medicine (A.H., J.J.F.B.), Ninewells Hospital and Medical School, Dundee, UK. * To whom correspondence should be addressed. E-mail: a.d.struthers{at}dundee.ac.uk.
Background—Increased oxidative stress in chronic heart failure is thought to contribute to endothelial dysfunction. Xanthine oxidase produces oxidative stress and therefore we examined whether allopurinol improved endothelial dysfunction in chronic heart failure. Methods and Results—We performed a randomized, placebo-controlled, double-blind crossover study on 11 patients with New York Heart Association class II-III chronic heart failure, comparing 300 mg allopurinol daily (1 month) versus placebo. Endothelial function was assessed by standard forearm venous occlusion plethysmography with acetylcholine, nitroprusside, and verapamil. Plasma malondialdehyde levels were also compared to assess significant changes in oxidative stress. Allopurinol significantly increased the forearm blood flow response to acetylcholine (percentage change in forearm blood flow [mean±SEM]: 181±19% versus 120±22% allopurinol versus placebo; P=0.003). There were no significant differences in the forearm blood flow changes between the placebo and allopurinol treatment arms with regard to sodium nitroprusside or verapamil. Plasma malondialdehyde was significantly reduced with allopurinol treatment (346±128 nmol/L versus 461±101 nmol/L, allopurinol versus placebo; P=0.03), consistent with reduced oxidative stress with allopurinol therapy. Conclusions—We have shown that allopurinol improves endothelial dysfunction in chronic heart failure. This raises the distinct possibility that allopurinol might reduce cardiovascular events and even improve exercise capacity in chronic heart failure.
Revised on May 1, 2002
Accepted on May 1, 2002
Allopurinol Improves Endothelial Dysfunction in Chronic Heart Failure
Colin A.J. Farquharson MBChB, MRCP(UK),
Key words: antioxidants • heart failure • exercise • endothelium
This article has been cited by other articles:
 |
|
 |
|
  C. Rinat, R. Becker-Cohen, A. Nir, S. Feinstein, D. Shemesh, N. Algur, E. Ben Shalom, B. Farber, and Y. Frishberg A comprehensive study of cardiovascular risk factors, cardiac function and vascular disease in children with chronic renal failure Nephrol. Dial. Transplant., November 23, 2009; (2009) gfp570v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Zhang, K. Sun, Y. Yang, H. Zhang, F. B. Hu, and R. Hui Plasma Uric Acid and Hypertension in a Chinese Community: Prospective Study and Metaanalysis Clin. Chem., November 1, 2009; 55(11): 2026 - 2034. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Riches, A. F. Wright, and S. H. Ralston Recent insights into the pathogenesis of hyperuricaemia and gout Hum. Mol. Genet., October 15, 2009; 18(R2): R177 - R184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Luk, G. P. Levin, E. E. Moore, X.-H. Zhou, B. R. Kestenbaum, and H. K. Choi Allopurinol and mortality in hyperuricaemic patients Rheumatology, July 1, 2009; 48(7): 804 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bergamini, M. Cicoira, A. Rossi, and C. Vassanelli Oxidative stress and hyperuricaemia: pathophysiology, clinical relevance, and therapeutic implications in chronic heart failure Eur J Heart Fail, May 1, 2009; 11(5): 444 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Navaneethan and S. Beddhu Associations of serum uric acid with cardiovascular events and mortality in moderate chronic kidney disease Nephrol. Dial. Transplant., April 1, 2009; 24(4): 1260 - 1266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nambiar, S. Viswanathan, B. Zachariah, N. Hanumanthappa, and Sridhar Gopalakrishna Magadi Oxidative Stress in Prehypertension: Rationale for Antioxidant Clinical Trials Angiology, April 1, 2009; 60(2): 221 - 234. [Abstract] [PDF]
|
|
|
|
 |
|
 J. P. Forman, H. Choi, and G. C. Curhan Fructose and Vitamin C Intake Do Not Influence Risk for Developing Hypertension J. Am. Soc. Nephrol., April 1, 2009; 20(4): 863 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hori and K. Nishida Oxidative stress and left ventricular remodelling after myocardial infarction Cardiovasc Res, February 15, 2009; 81(3): 457 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Godbole, X. Lu, X. Guo, and G. S. Kassab NADPH oxidase has a directional response to shear stress Am J Physiol Heart Circ Physiol, January 1, 2009; 296(1): H152 - H158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. I. Feig, D.-H. Kang, and R. J. Johnson Uric Acid and Cardiovascular Risk N. Engl. J. Med., October 23, 2008; 359(17): 1811 - 1821. [Full Text] [PDF]
|
|
|
|
 |
|
 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 JAMA, August 27, 2008; 300(8): 924 - 932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Alcaino, D. Greig, M. Chiong, H. Verdejo, R. Miranda, R. Concepcion, J. L. Vukasovic, G. Diaz-Araya, R. Mellado, L. Garcia, et al. Serum uric acid correlates with extracellular superoxide dismutase activity in patients with chronic heart failure Eur J Heart Fail, July 1, 2008; 10(7): 646 - 651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Luque-Ramirez, F. Alvarez-Blasco, M. G. Uriol Rivera, and H. F. Escobar-Morreale Serum uric acid concentration as non-classic cardiovascular risk factor in women with polycystic ovary syndrome: effect of treatment with ethinyl-estradiol plus cyproterone acetate versus metformin Hum. Reprod., July 1, 2008; 23(7): 1594 - 1601. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Hare, B. Mangal, J. Brown, C. Fisher Jr, R. Freudenberger, W. S. Colucci, D. L. Mann, P. Liu, M. M. Givertz, R. P. Schwarz, et al. Impact of oxypurinol in patients with symptomatic heart failure. Results of the OPT-CHF study. J. Am. Coll. Cardiol., June 17, 2008; 51(24): 2301 - 2309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.H. W. Tang The ongoing search for a stratified medicine approach in heart failure. J. Am. Coll. Cardiol., June 17, 2008; 51(24): 2310 - 2312. [Full Text] [PDF]
|
|
|
|
|
|
R. Dworakowski, S. Walker, A. Momin, J. Desai, A. El-Gamel, O. Wendler, M. T. Kearney, and A. M. Shah Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Derived Superoxide and Vascular Endothelial Dysfunction in Human Heart Failure J. Am. Coll. Cardiol., April 8, 2008; 51(14): 1349 - 1356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J Johnson, M. S Segal, Y. Sautin, T. Nakagawa, D. I Feig, D.-H. Kang, M. S Gersch, S. Benner, and L. G Sanchez-Lozada Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease Am. J. Clinical Nutrition, October 1, 2007; 86(4): 899 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. K. Choi and G. Curhan Independent Impact of Gout on Mortality and Risk for Coronary Heart Disease Circulation, August 21, 2007; 116(8): 894 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Seddon, Y. H Looi, and A. M Shah Oxidative stress and redox signalling in cardiac hypertrophy and heart failure Heart, August 1, 2007; 93(8): 903 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Landmesser, S. Spiekermann, C. Preuss, S. Sorrentino, D. Fischer, C. Manes, M. Mueller, and H. Drexler Angiotensin II Induces Endothelial Xanthine Oxidase Activation: Role for Endothelial Dysfunction in Patients With Coronary Disease Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 943 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. Sanchez-Lozada, E. Tapia, R. Lopez-Molina, T. Nepomuceno, V. Soto, C. Avila-Casado, T. Nakagawa, R. J. Johnson, J. Herrera-Acosta, and M. Franco Effects of acute and chronic L-arginine treatment in experimental hyperuricemia Am J Physiol Renal Physiol, April 1, 2007; 292(4): F1238 - F1244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. George, E. Carr, J. Davies, J.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, December 5, 2006; 114(23): 2508 - 2516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Zimmet and J. M. Hare Nitroso-Redox Interactions in the Cardiovascular System Circulation, October 3, 2006; 114(14): 1531 - 1544. [Full Text] [PDF]
|
|
|
|
|
|
C. E. Murdoch, M. Zhang, A. C. Cave, and A. M. Shah NADPH oxidase-dependent redox signalling in cardiac hypertrophy, remodelling and failure Cardiovasc Res, July 15, 2006; 71(2): 208 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ruggiero, A. Cherubini, A. Ble, A. J.G. Bos, M. Maggio, V. D. Dixit, F. Lauretani, S. Bandinelli, U. Senin, and L. Ferrucci Uric acid and inflammatory markers Eur. Heart J., May 2, 2006; 27(10): 1174 - 1181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. El Solh, R. Saliba, T. Bosinski, B. J. B. Grant, E. Berbary, and N. Miller Allopurinol improves endothelial function in sleep apnoea: a randomised controlled study. Eur. Respir. J., May 1, 2006; 27(5): 997 - 1002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zoccali, R. Maio, F. Mallamaci, G. Sesti, and F. Perticone Uric Acid and Endothelial Dysfunction in Essential Hypertension J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1466 - 1471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Eskurza, Z. D. Kahn, and D. R. Seals Xanthine oxidase does not contribute to impaired peripheral conduit artery endothelium-dependent dilatation with ageing J. Physiol., March 15, 2006; 571(3): 661 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pacher, A. Nivorozhkin, and C. Szabo Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol. Rev., March 1, 2006; 58(1): 87 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-H. Kang, S.-K. Park, I.-K. Lee, and R. J. Johnson Uric Acid-Induced C-Reactive Protein Expression: Implication on Cell Proliferation and Nitric Oxide Production of Human Vascular Cells J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3553 - 3562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Kittleson and J. M. Hare Xanthine oxidase inhibitors: an emerging class of drugs for heart failure Eur. Heart J., August 1, 2005; 26(15): 1458 - 1460. [Full Text] [PDF]
|
|
|
|
|
|
J. S. McNally, A. Saxena, H. Cai, S. Dikalov, and D. G. Harrison Regulation of Xanthine Oxidoreductase Protein Expression by Hydrogen Peroxide and Calcium Arterioscler Thromb Vasc Biol, August 1, 2005; 25(8): 1623 - 1628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W Doehner and S D Anker Xanthine oxidase inhibition for chronic heart failure: is allopurinol the next therapeutic advance in heart failure? Heart, June 1, 2005; 91(6): 707 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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, June 1, 2005; 91(6): 749 - 753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Reyes The increase in serum uric acid concentration caused by diuretics might be beneficial in heart failure Eur J Heart Fail, June 1, 2005; 7(4): 461 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. F.H. Mueller, K. Laude, J. S. McNally, and D. G. Harrison Redox Mechanisms in Blood Vessels Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): 274 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bonaventura and A. Gow NO and superoxide: Opposite ends of the seesaw in cardiac contractility PNAS, November 23, 2004; 101(47): 16403 - 16404. [Full Text] [PDF]
|
|
|
|
 |
|
 J.-M. Li and A. M Shah Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2004; 287(5): R1014 - R1030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Engberding, S. Spiekermann, A. Schaefer, A. Heineke, A. Wiencke, M. Muller, M. Fuchs, D. Hilfiker-Kleiner, B. Hornig, H. Drexler, et al. Allopurinol Attenuates Left Ventricular Remodeling and Dysfunction After Experimental Myocardial Infarction: A New Action for an Old Drug? Circulation, October 12, 2004; 110(15): 2175 - 2179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.-P. Xu, M.-S. Chen, Y.-Z. Wang, Q. Yi, S.-B. Lin, A. F. Chen, and J.-D. Luo Leptin Induces Hypertrophy via Endothelin-1-Reactive Oxygen Species Pathway in Cultured Neonatal Rat Cardiomyocytes Circulation, September 7, 2004; 110(10): 1269 - 1275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Kelley, A. Trostchansky, H. Rubbo, B. A. Freeman, R. Radi, and M. M. Tarpey Binding of Xanthine Oxidase to Glycosaminoglycans Limits Inhibition by Oxypurinol J. Biol. Chem., September 3, 2004; 279(36): 37231 - 37234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J E Macdonald, N Kennedy, and A D Struthers Effects of spironolactone on endothelial function, vascular angiotensin converting enzyme activity, and other prognostic markers in patients with mild heart failure already taking optimal treatment Heart, July 1, 2004; 90(7): 765 - 770. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Wright, L. A. Ginger, N. Kosila, N. D. Elkins, B. Essary, J. L. McManaman, and J. E. Repine Mononuclear Phagocyte Xanthine Oxidoreductase Contributes to Cytokine-Induced Acute Lung Injury Am. J. Respir. Cell Mol. Biol., April 1, 2004; 30(4): 479 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Berry and J. M. Hare Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications J. Physiol., March 15, 2004; 555(3): 589 - 606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. A. Wilmer, B. H. Rovin, C. J. Hebert, S. V. Rao, K. Kumor, and L. A. Hebert Management of Glomerular Proteinuria: A Commentary J. Am. Soc. Nephrol., December 1, 2003; 14(12): 3217 - 3232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kogler, H. Fraser, S. McCune, R. Altschuld, and E. Marban Disproportionate enhancement of myocardial contractility by the xanthine oxidase inhibitor oxypurinol in failing rat myocardium Cardiovasc Res, September 1, 2003; 59(3): 582 - 592. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Johnson, D.-H. Kang, D. Feig, S. Kivlighn, J. Kanellis, S. Watanabe, K. R. Tuttle, B. Rodriguez-Iturbe, J. Herrera-Acosta, and M. Mazzali Is There a Pathogenetic Role for Uric Acid in Hypertension and Cardiovascular and Renal Disease? Hypertension, June 1, 2003; 41(6): 1183 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Hare and R. J. Johnson Uric Acid Predicts Clinical Outcomes in Heart Failure: Insights Regarding the Role of Xanthine Oxidase and Uric Acid in Disease Pathophysiology Circulation, April 22, 2003; 107(15): 1951 - 1953. [Full Text] [PDF]
|
|
|
|
|
|
S. Guthikonda, C. Sinkey, T. Barenz, and W. G. Haynes Xanthine Oxidase Inhibition Reverses Endothelial Dysfunction in Heavy Smokers Circulation, January 28, 2003; 107(3): 416 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Landmesser and H. Drexler Allopurinol and Endothelial Function in Heart Failure: Future or Fantasy? Circulation, July 9, 2002; 106(2): 173 - 175. [Full Text] [PDF]
|
|