Allopurinol Normalizes Endothelial Dysfunction in Type 2 Diabetics With Mild Hypertension
Abstract
Abstract —Therapeutic strategies against free radicals have mostly focused on the augmentation of antioxidant defenses (eg, vitamins C and E). A novel approach is to prevent free radical generation by the enzyme system xanthine oxidase. We examined whether the inhibition of xanthine oxidase with allopurinol can improve endothelial function in subjects with type 2 diabetes and coexisting mild hypertension compared with control subjects of a similar age. We examined 23 subjects (11 patients with type 2 diabetes and 12 healthy age-matched control subjects) in 2 parallel groups. The subjects were administered 300 mg allopurinol in a randomized, placebo-controlled study in which both therapies were administered for 1 month. Endothelial function was assessed with bilateral venous occlusion plethysmography, in which the forearm blood flow responses to intra-arterial infusions of endothelium-dependent and -independent vasodilators were measured. Allopurinol significantly increased the mean forearm blood flow response to acetylcholine by 30% (3.16±1.21 versus 2.54±0.76 mL · 100 mL −1 · min −1 allopurinol versus placebo; P =0.012, 95% CI 0.14, 1.30) but did not affect the nitroprusside response in patients with type 2 diabetes. There was no significant impact on either endothelium-dependent or -independent vascular responses in age-matched control subjects. Allopurinol improved endothelial function to near-normal levels. Regarding markers of free radical activity, the level of malondialdehyde was significantly reduced (0.30±0.04 versus 0.34±0.05 μmol/L for allopurinol versus placebo, P =0.03) in patients with type 2 diabetes but not in control subjects. The xanthine oxidase inhibitor allopurinol improves endothelial dysfunction in patients with type 2 diabetes with mild hypertension but not in matched control subjects. In the former group, allopurinol restored endothelial function to near-normal levels.
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Extensive evidence supports a role of XO in the development of cardiovascular disease.
“Extensive evidence supports a role of XO in the development of cardiovascular disease (137, 148, 157, 282, 430, 466, 561, 633).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [137]
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- Authors
- Butler, R., Morris, A. D., Belch, J. J. F., Hill, A., & Struthers, A. D.
- Affiliations
- Ninewells Hospital (GB)
- Venue
- Hypertension
- Published
- 2000-03
- Volume
- 35
- Issue
- 3
- Pages
- 746-751
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2169190847
- Cited by
- 463
- References
- 39
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 9 · 2023: 9 · 2022: 16 · 2021: 11 · 2020: 17 · 2019: 18 · 2018: 13 · 2017: 22 · 2016: 21 · 2015: 19 · 2014: 26 · 2013: 21 · 2012: 25
- FWCI
- 9.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Funders
- British Heart Foundation
- Tenovus
- 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, type 2 diabetes, mild hypertension, xanthine oxidase inhibition, free radicals, malondialdehyde, acetylcholine-induced vasodilation, forearm blood flow, nitric oxide
- MeSH terms
- Age Factors, Aged, Allopurinol, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Endothelium, Vascular, Enzyme Inhibitors, Female, Forearm, Glycated Hemoglobin, Humans, Hypertension, Male, Malondialdehyde, Middle Aged, Nitroprusside, Plethysmography, Regional Blood Flow, Regression Analysis, Vasodilator Agents, Xanthine Oxidase, Free Radical Scavengers
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