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dc.contributor.authorWaring, William Stephenen
dc.date.accessioned2018-01-31T11:39:46Z
dc.date.available2018-01-31T11:39:46Z
dc.date.issued2005
dc.identifier.urihttp://hdl.handle.net/1842/27617
dc.description.abstracten
dc.description.abstractBackground There are strong epidemiological associations between high serum uric acid concentrations and increased cardiovascular risk. However, it is unclear if uric acid is an independent causal risk factor, serves a protective role due to its antioxidant properties, or simply acts as a passive marker of risk through association with other factors. The distinction is important because, if acting as a causal risk factor, treatment to lower uric acid concentrations might reduce cardiovascular risk.en
dc.description.abstractAims: To study the cardiovascular effects of raising and lowering circulating uric acid concentrations, so as to identify potential mechanisms by which uric acid could impair cardiovascular function or, as an antioxidant, serve a protective role.en
dc.description.abstractMethods: I developed a technique of uric acid administration that allowed the effects of raised concentrations to be examined in vivo. The potential impact on serum antioxidant capacity, plasma viscosity, platelet aggregability, systemic haemodynamics, baroreflex sensitivity, large arterial stiffness, and endothelial function were studied in healthy subjects. The effects of high uric acid concentrations were studied in a model of acute exercise-induced oxidative stress, and in regular smokers and patients with type 1 diabetes who are ordinarily exposed to chronic oxidative stress. The effects of lowering uric acid, by means of urate oxidase, were studied in patients with type 2 diabetes to explore whether this might improve vascular function in these patients.en
dc.description.abstractResults: Raising and lowering uric acid concentrations had no effect on vascular function in healthy subjects. Uric acid administration significantly increased serum antioxidant capacity, reduced oxidative stress during acute aerobic exercise, and improved endothelium-dependent vascular responses in regular smokers and patients with type 1 diabetes. Lowering uric acid concentrations did not influence vascular function in healthy subjects or patients with type 2 diabetes.en
dc.description.abstractConclusions: High uric acid concentrations did not impair vascular function, at least in the acute situation, and appear to preserve vascular function by protecting against oxidative stress in smokers and patients with type 1 diabetes. These findings do not support a causal link between high serum uric acid concentrations and increased cardiovascular risk. Further research is required to define the mechanisms by which high uric acid concentrations ameliorate endothelial dysfunction, and to examine whether these properties have therapeutic potential in diseases characterised by oxidative stress.en
dc.publisherThe University of Edinburghen
dc.relation.ispartofAnnexe Thesis Digitisation Project 2017 Block 16en
dc.relation.isreferencedbyen
dc.titleAn investigation of the potential influence of serum uric acid concentration on regulation of the human cardiovascular systemen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelen
dc.type.qualificationnamePhD Doctor of Philosophyen


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