ABSTRACT
OBJECTIVE: To investigate the possibility that uric acid (UA) can impair endothelial function, an important surrogate for atherosclerosis. DESIGN: UA was administered locally or systemically to healthy adult men and women in a series of randomised placebo controlled studies. This temporarily raised serum UA concentrations, so that the potential effects of hyperuricaemia on mechanisms of cardiovascular disease could be studied. MAIN OUTCOME MEASURES: The effects of UA administration on basal blood flow and responses to locally administered acetylcholine, sodium nitroprusside, and L-N(G)-monomethylarginine were studied in the forearm vascular bed with venous occlusion plethysmography. The effects of hyperuricaemia on systemic vascular resistance, large artery compliance, and baroreflex sensitivity were examined by validated non-invasive techniques. RESULTS: UA administration caused a twofold increase in serum concentrations. However, there were no acute effects on haemodynamic variables, basal forearm blood flow, or nitric oxide dependent endothelial function. CONCLUSION: Unlike other risk factors associated with endothelial dysfunction, acute exposure to high concentrations of UA does not impair cardiovascular function in healthy men. These findings do not support a causal link between hyperuricaemia and atherosclerosis.
