Higher levels of serum
uric acid are independently associated with endothelial dysfunction, a mechanism for incident
hypertension.
Overweight/obese individuals are more prone to endothelial dysfunction than their lean counterparts. However, the effect of lowering serum
uric acid on endothelial dysfunction in these individuals has not been examined thoroughly. In this randomized, double-blind, placebo-controlled trial of nonhypertensive,
overweight, or obese individuals with higher serum
uric acid (body mass index ≥25 kg/m2 and serum
uric acid ≥5.0 mg/dL), we assigned subjects to
probenecid (500-1000 mg/d),
allopurinol (300-600 mg/d), or matching placebo. The primary outcome was endothelium-dependent vasodilation measured by brachial artery ultrasound at baseline and 8 weeks. By the end of the trial, 47, 49, and 53 participants had been allocated to receive
probenecid,
allopurinol, and placebo, respectively. Mean serum
uric acid levels significantly decreased in the
probenecid (from 6.1 to 3.5 mg/dL) and
allopurinol groups (from 6.1 to 2.9 mg/dL) but not in the placebo group (6.1 to 5.6 mg/dL). None of the interventions produced any significant change in endothelium-dependent vasodilation (
probenecid, 7.4±5.1% at baseline and 8.3±5.1% at 8 weeks;
allopurinol, 7.6±6.0% at baseline and 6.2±4.8% at 8 weeks; and placebo, 6.5±3.8% at baseline and 7.1±4.9% at 8 weeks). In this randomized, double-blind, placebo-controlled trial,
uric acid lowering did not affect endothelial function in
overweight or obese nonhypertensive individuals. These data do not support the hypothesis that
uric acid is causally related to endothelial dysfunction, a potential mechanism for development of
hypertension.