title: Allopurinol improves endothelial function in sleep apnoea: a randomised controlled study.
abstract: Increased oxidative stress in obstructive sleep apnoea is thought to contribute to endothelial dysfunction. The objective of this study was to test the hypothesis that inhibition of xanthine oxidase by allopurinol can improve endothelial function in patients with obstructive sleep apnoea. A randomised double-blind placebo-controlled crossover study was performed on 12 patients with moderate-to-severe obstructive sleep apnoea, comparing 300 mg allopurinol daily for 2 weeks with placebo. Endothelial function was assessed using hyperaemia-induced flow-mediated vasodilation (FMD) at baseline and following treatment. Plasma malondialdehyde levels were compared in order to assess significant changes in oxidative stress. Baseline FMD correlated significantly with the severity of sleep apnoea and the time spent with an arterial oxygen saturation of <90%. Allopurinol caused a significant increase in FMD compared to placebo (10.4+/-3.2 versus 7.4+/-2.8%, respectively). Plasma malondialdehyde levels were significantly reduced with allopurinol treatment (1.5+/-0.3 versus 1.2+/-0.3 micromol.L(-1)), consistent with reduced oxidative stress. Allopurinol improves endothelial dysfunction in patients with moderate-to-severe obstructive sleep apnoea. These observations suggest that xanthine oxidase contributes significantly to vasodilatory impairment.
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Dept of Medicine, School of Medicine and Biomedical Sciences and Veterans Affairs Medical Center, University at Buffalo, Buffalo, NY, USA. solh@buffalo.edu
authors.forename: A A
authors.initials: AA
authors.lastname: El Solh
authors.forename: R
authors.initials: R
authors.lastname: Saliba
authors.forename: T
authors.initials: T
authors.lastname: Bosinski
authors.forename: B J B
authors.initials: BJ
authors.lastname: Grant
authors.forename: E
authors.initials: E
authors.lastname: Berbary
authors.forename: N
authors.initials: N
authors.lastname: Miller
mesh_terms: D000328:Adult; D000493:Allopurinol / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012891:Sleep Apnea Syndromes / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D004791:Enzyme Inhibitors; D000493:Allopurinol