Allopurinol Improves Endothelial Dysfunction in Chronic Heart Failure
Abstract
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.
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In small trials, pharmacological inhibition of XO with allopurinol/oxypurinol improved cardiovascular conditions in heart failure, dilated cardiomyopathy, and diabetes.
“In small trials, the pharmacological inhibition of XO with allopurinol/oxypurinol improved cardiovascular conditions in several pathologies, including heart failure (58, 278), dilated cardiomyopathy (148), and diabetes (137, 224).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [278]
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Self-citation
- Authors
- Farquharson, C. A. J., Butler, R., Hill, A., Belch, J. J. F., & Struthers, A. D.
- Affiliations
- Ninewells Hospital (GB)
- Venue
- Circulation
- Published
- 2002-07-09
- Volume
- 106
- Issue
- 2
- Pages
- 221-226
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1977110551
- Cited by
- 504
- References
- 34
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 15 · 2023: 12 · 2022: 16 · 2021: 16 · 2020: 22 · 2019: 19 · 2018: 25 · 2017: 17 · 2016: 16 · 2015: 20 · 2014: 25 · 2013: 31 · 2012: 26
- FWCI
- 13.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Funders
- British Heart Foundation
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- allopurinol, endothelial dysfunction, chronic heart failure, xanthine oxidase, oxidative stress, malondialdehyde, forearm blood flow, acetylcholine response, nitric oxide, verapamil, exercise capacity
- MeSH terms
- Aged, Allopurinol, Antioxidants, Blood Pressure, Chronic Disease, Double-Blind Method, Endothelium, Vascular, Enzyme Inhibitors, Female, Forearm, Heart Failure, Heart Rate, Humans, Male, Malondialdehyde, Regional Blood Flow, Vasodilator Agents, Xanthine Oxidase, Cross-Over Studies
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