title: Uric acid restores endothelial function in patients with type 1 diabetes and regular smokers.
abstract: Endothelial dysfunction is a characteristic finding in both patients with type 1 diabetes and in regular smokers and is an important precursor to atherosclerosis. The urate molecule has antioxidant properties, which could influence endothelial function. The impact of acutely raising uric acid concentrations on endothelial function was studied in eight men with type 1 diabetes, eight healthy regular smokers, and eight age-matched healthy control subjects in a randomized, four-way, double-blind, placebo-controlled study. Subjects received 1,000 mg uric acid i.v. in vehicle, 1,000 mg vitamin C as a control antioxidant, vehicle alone, or 0.9% saline on separate occasions over 1 h. Forearm blood flow responses to intrabrachial acetylcholine and sodium nitroprusside were assessed using venous occlusion plethysmography. Responses to acetylcholine, but not sodium nitroprusside, were impaired in patients with diabetes (P < 0.001) and in smokers (P < 0.005) compared with control subjects. Administration of uric acid and vitamin C selectively improved acetylcholine responses in patients with type 1 diabetes (P < 0.01) and in regular smokers (P < 0.05). Uric acid administration improved endothelial function in the forearm vascular bed of patients with type 1 diabetes and smokers, suggesting that high uric acid concentrations in vivo might serve a protective role in these and other conditions associated with increased cardiovascular risk.
authors.affiliation: Clinical Pharmacology Unit, University of Edinburgh, The Queen's Medical Research Institute, 3rd Floor East, Room E3.22, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. s.waring@ed.ac.uk
authors.forename: W Stephen
authors.initials: WS
authors.lastname: Waring
authors.forename: John A
authors.initials: JA
authors.lastname: McKnight
authors.forename: David J
authors.initials: DJ
authors.lastname: Webb
authors.forename: Simon R J
authors.initials: SR
authors.lastname: Maxwell
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D005542:Forearm / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010919:Placebos; D012016:Reference Values; D012907:Smoking / Q000503:physiopathology*; D014527:Uric Acid / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D010919:Placebos; D009599:Nitroprusside; D014527:Uric Acid; D000109:Acetylcholine; D001205:Ascorbic Acid