Journal Article

Uric Acid Restores Endothelial Function in Patients With Type 1 Diabetes and Regular Smokers

John A. McKnight, Simon R.J. Maxwell, David J. Webb, W. Stephen Waring

2006

Overview

Uric Acid Restores Endothelial Function in Patients With Type 1 Diabetes and Regular Smokers W. Stephen Waring 1 , John A. McKnight 2 , David J. Webb 1 and Simon R.J. Maxwell 1 1 Clinical Pharmacology Unit, The Queen’s Medical Research Institute, The University of Edinburgh, Scotland, U.K 2 Department of Diabetes, Western General Hospital, Edinburgh, U.K Address correspondence and reprint requests to W.S. Waring, 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, U.K. E-mail: s.waring{at}ed.ac.uk 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. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted August 16, 2006. Received February 28, 2006. DIABETES

• Publisher: American Diabetes Association
• Subject: Acetylcholine - pharmacology / Adult / Antioxidants / Antioxidants - pharmacology / Ascorbic Acid - pharmacology / Atherosclerosis / Biological and medical sciences / Blood Flow Velocity - drug effects / Blood Pressure - drug effects / Body Mass Index / Cardiovascular disease / Care and treatment / Cross-Over Studies / Diabetes / Diabetes Mellitus, Type 1 - physiopathology / Diabetes. Impaired glucose tolerance / Double-Blind Method / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Endothelium, Vascular - drug effects / Endothelium, Vascular - physiology / Endothelium, Vascular - physiopathology / Etiopathogenesis. Screening. Investigations. Target tissue resistance / Forearm - blood supply / Free radicals / Genetic aspects / Health aspects / Heart Rate - drug effects / Humans / Male / Medical sciences / Nitric oxide / Nitroprusside - pharmacology / Oxidative stress / Placebos / Reference Values / Smoking - physiopathology / Type 1 diabetes / Uric acid / Uric Acid - pharmacology / Uric Acid - therapeutic use / Vitamin C