Effects of uric acid on vascular endothelial function from bedside to bench.
Level 4 - case-series / case-control
Cross-sectional clinical observation in a single outpatient cohort combined with in vitro laboratory experiments
PubMed 30185927 · doi:10.1038/s41440-018-0095-4
What was done
Researchers measured reactive hyperemia peripheral arterial tonometry (EndoPAT 2000) and serum uric acid levels in 92 hypertensive outpatients. The cohort was split into a high-risk group with complications (cardiovascular disease, cerebrovascular disease, chronic kidney disease, and/or diabetes; n = 51) and a low-risk group without these complications (n = 41). An in vitro study in human umbilical vein endothelial cells evaluated cell viability via WST-8 assay and endothelial nitric oxide synthase (eNOS) phosphorylation via Western blot under hypoxic conditions with uric acid and ascorbic acid treatments.
What was found
In the total cohort (n = 92) and high-risk group (n = 51), reactive hyperemia index (RHI) showed no significant correlation with serum uric acid (R = -0.125, P = 0.235 and R = -0.025, P = 0.860, respectively). In the low-risk group (n = 41), RHI correlated negatively with serum uric acid (R = -0.335, P = 0.032), and serum uric acid predicted RHI independently of age, BMI, systolic blood pressure, and LDL cholesterol on multiple regression (R = -0.321, P = 0.043). In vitro, hypoxia reduced cell viability, which decreased further with uric acid and improved with ascorbic acid; uric acid also reduced eNOS phosphorylation during hypoxia.
Why it matters
This study suggests that uric acid may impair peripheral endothelial function in early-stage or uncomplicated hypertension, supporting further interventional trials of urate-lowering therapies.
Limits
The human sample size was small (n = 92 overall, n = 41 in the subgroup showing the correlation), and the cross-sectional design cannot establish causality. The in vitro findings rely on acute hypoxic cell culture models that may not reflect chronic in vivo vascular conditions.
Cited by
- supports Uric acid is an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), which contributes to elevated blood pressure.