High-dose allopurinol improves endothelial function by profoundly reducing vascular oxidative stress and not by lowering uric acid
| Autor: | Elaine Carr, Jacob George, Jill J. F. Belch, Allan D. Struthers, Justine Davies |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Nitroprusside medicine.medical_specialty Endothelium Allopurinol Vasodilator Agents Urology Cardiac Output Low Blood Pressure Ascorbic Acid Placebo chemistry.chemical_compound Double-Blind Method Physiology (medical) medicine Humans Enzyme Inhibitors Xanthine oxidase Aged Cross-Over Studies Dose-Response Relationship Drug business.industry Probenecid Middle Aged Uricosuric Agents medicine.disease Crossover study Acetylcholine Surgery Uric Acid Oxidative Stress medicine.anatomical_structure chemistry Regional Blood Flow Heart failure Uric acid Female Endothelium Vascular Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Circulation. 114(23) |
| ISSN: | 1524-4539 |
| Popis: | Background— Allopurinol has been shown to improve endothelial function in chronic heart failure. This study aimed to establish its mechanism of action and to construct a dose–response curve for the effect of allopurinol. Methods and Results— Two randomized, placebo-controlled, double-blind, crossover studies were performed for 1 month on patients with New York Heart Association Class II–III chronic heart failure, comparing 300 mg allopurinol, 600 mg allopurinol, and placebo for the first study and 1000 mg probenecid versus placebo in the second study. Endothelial function was assessed by standard forearm venous occlusion plethysmography. Allopurinol 600 mg/d significantly increased forearm blood flow response to acetylcholine compared with both allopurinol 300 mg/d and placebo (% change in forearm blood flow [mean±SEM]: 240.31±38.19% versus 152.10±18.21% versus 73.96±10.29%, P Conclusions— For the first time, we have shown that a steep dose–response relationship exists between allopurinol and its effect on endothelial function. We also showed that the mechanism of improvement in endothelial function with allopurinol lies in its ability to reduce vascular oxidative stress and not in urate reduction. The reduction in vascular oxidative stress was profound because high-dose allopurinol totally abolished the oxidative stress that was sensitive to the high-dose vitamin C that was used in this study. |
| Databáze: | OpenAIRE |
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