Recent experimental findings have led to renewed interest in the possible role of uric acid in the pathogenesis of both hypertension and vascular disease. Often considered an antioxidant, biochemical and in vitro data indicate that noncrystalline, soluble uric acid also can react to form radicals, increase lipid oxidation, and induce various pro-oxidant effects in vascular cells. In vitro and in vivo findings suggest that uric acid may contribute to endothelial dysfunction by inducing antiproliferative effects on endothelium and impairing nitric oxide production. Proinflammatory and proliferative effects of soluble uric acid have been described on vascular smooth muscle cells (VSMCs), and in animal models of mild hyperuricemia, hypertension develops in association with intrarenal vascular disease. Possible adverse effects of uric acid on the vasculature have been linked to increased chemokine and cytokine expression, induction of the renin-angiotensin system, and to increased vascular C-reactive protein (CRP) expression. Experimental evidence suggests a complex but potentially direct causal role for uric acid in the pathogenesis of hypertension and atherosclerosis.
Bibliographical noteFunding Information:
Supported in part by National Institutes of Health grants DK-52121 and HL-68607; the George O’Brien Center (1P50-DK064233-01); National Health and Medical Research Council, Australia; Don and Lorraine Jacquot Fellowship and Jacquot Research Establishment Awards, Australia (J.K.); and grant R04-2002-000-00183-0 from the Basic Research Program of the Korea Science and Engineering Foundation (D.-H.K.).