Uric acid and the development of hypertension.

Uric acid is a major product of purine metabolism in humans. Epidemiologic and experimental evidence suggests that serum uric acid is an independent risk factor for developing hypertension. Several plausible mechanisms have been proposed to explain how hyperuricemia is related to hypertension. In this review we summarize the current understanding concerning uric acid and the development of hypertension based on a MEDLINE search of all peer-review publications (original articles and reviews) on this topic between 1965 and 2009, focusing on papers published in the last 2 decades. The results from animal studies and clinical observations support renal microvascular and tubulointerstitial injury being the key to uric acid-induced hypertension. Associations with other systemic derangements, including endothelial dysfunction, low-level systemic inflammation, sympathetic overactivity and insulin resistance, render uric acid to a complex but potentially direct causal role in the pathogenesis of hypertension. The identification of conceivable biological mechanisms by which uric acid could cause high blood pressure has led to new insights about therapeutic modalities that may control high blood pressure and cardiovascular outcomes. Although there is still no consensus on the treatment of individuals with asymptomatic hyperuricemia, it is time to reappraise potential approaches for these subjects with regard to prevention of hypertension and related renal and cardiovascular complications.