Abstract
Hyperuricemia during hypertension is associated with aberrant vascular functions and increased oxidative stress, which affects endothelial dysfunction. Nevertheless, the molecular mechanisms underlying the effects of uric acid on vascular smooth muscle cells (VSMCs) through oxidative stress remain unclear. The aim of the present study was to investigate the dose- and time-dependent effects of uric acid on oxidative stress and p53 protein expression in VSMCs. VSMCs were incubated with various concentrations of uric acid (0-50 mg/dl) for different time periods (1-24 h). Thiobarbituric acid reactive substances (TBARs), protein carbonylation and nitric oxide (NO) levels were determined using appropriate assay kits. Superoxide anion release was detected using the Görlach method. Western blotting was performed to determine the protein expression levels of p53. The findings demonstrated that the application of uric acid led to an increase in protein carbonylation and superoxide anion levels while causing a decrease in NO levels. Conversely, no significant effect was observed on TBARS levels. Additionally, it was observed that high concentrations of uric acid suppressed p53 expression at 6, 12 and 24 h. The present study provided evidence that the influence of uric acid on oxidative stress was more closely associated with time than dose; however, not all effects observed were strictly time-dependent.