Abstract
Uric acid is associated with hypertension and increased renin-angiotensin system activity, although this relationship diminishes after chronic exposure to high levels. Uric acid is more strongly associated with poor outcomes in women compared to men, although whether this is due to a sex-specific uric acid-mediated pathophysiology or reflects sex differences in baseline uric acid levels remains unknown. We examined the association between uric acid and vascular measures at baseline and in response to angiotensin-II challenge in young healthy humans. Fifty-two subjects (17 men, 35 premenopausal women) were studied in high-salt balance. Serum uric acid levels were significantly higher in men compared to women (328 ± 14 μmol/L vs. 248 ± 10 μmol/L, P < 0.001), although all values were within normal sex-specific range. Men demonstrated no association between uric acid and blood pressure, either at baseline or in response to angiotensin-II. In stark contrast, a significant association was observed between uric acid and blood pressure at baseline (systolic blood pressure, P = 0.005; diastolic blood pressure, P = 0.02) and in response to angiotensin-II (systolic blood pressure, P = 0.035; diastolic blood pressure, P = 0.056) in women. However, this sex difference lost significance after adjustment for baseline uric acid. When all subjects were stratified according to high (>300 μmol/L) or low (≤300 μmol/L) uric acid levels, only the low uric acid group showed a positive association between uric acid and measures of vascular tone at baseline and in response to angiotensin-II. Differences in uric acid-mediated outcomes between men and women likely reflect differences in exposure to increased uric acid levels, rather than a sex-specific uric acid-mediated pathophysiology.