Uric acid has been suspected to be a risk factor for
hypertension since the 1870s. Numerous epidemiological studies demonstrate an association between
uric acid and both incident and prevalent
hypertension in diverse populations. Studies in elderly patients have had more variable results, raising the possibility that
uric acid may be more significant to
hypertension in the young. Animal models support a two-phase mechanism for the development of hyperuricemic
hypertension. Initially,
uric acid induces vasoconstriction by activation of the renin-angiotensin system and reduction of circulating
nitric oxide, which can be reversed by lowering
uric acid. Over time,
uric acid uptake into vascular smooth muscle cells causes cellular proliferation and secondary
arteriolosclerosis that impairs pressure natriuresis, causing
sodium-sensitive
hypertension. Consistent with the animal model data, small clinical trials performed in adolescents with newly diagnosed
essential hypertension demonstrate that at least in certain young patients, reduction of serum
uric acid can mitigate blood pressure elevation. While more research is clearly necessary, the available data suggest that
uric acid is likely causative in some cases of early-onset
hypertension.