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Title: An investigation of the potential influence of serum uric acid concentration on regulation of the human cardiovascular system
Author: Waring, William Stephen
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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The studies described herein were designed to allow the potential influence of serum UA concentration on human cardiovascular function to be studied in vivo by means of administration of UA and urate oxidase to raise and lower circulating UA concentrations respectively. The objective was to identify mechanisms by which high UA concentrations could confer cardiovascular risk or, as an antioxidant, serve a protective role. I developed and refined a technique of UA administration, which allowed study of the potential effects of high UA concentrations on haemorheological factors, platelet aggregability, systemic haemodynamics, baroreflex sensitivity, large arterial stiffness, and in vivo endothelial function. The effect of raising UA concentrations on and serum antioxidant capacity were examined in healthy subjects, at rest and in an exercise-induced model of acute oxidative stress, and patients with type 1 diabetes and regular smokers who are ordinarily exposed to chronic oxidative stress. I performed a dose-finding study and administered urate oxidase, as a means of lowering UA, in healthy subjects and patients with type 2 diabetes to investigate the possibility that UA lowering might improve vascular function in this patient group. Neither raising nor lowering UA concentrations had any direct affect on vascular function in healthy people. Acute elevation of circulating UA concentrations is accompanied by increased serum antioxidant capacity, and reduced oxidative stress during aerobic exercise. Raising serum UA concentrations restored endothelial function in patients with type 1 diabetes and smokers, but had no effect in healthy subjects. Lowering UA concentrations did not influence vascular function in patients with type 2 diabetes or healthy subjects. The present findings do not support a causal link between high serum UA concentrations and increased cardiovascular risk. Additional research is required to further define the mechanisms by which high UA concentrations ameliorate endothelial dysfunction, and to examine whether these properties have therapeutic potential in diseases characterised by oxidative stress.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available