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Free Radic Res. 2013 Feb;47(2):82-8. doi: 10.3109/10715762.2012.747677. Epub 2012 Dec 4.

Uric acid modulates vascular endothelial function through the down regulation of nitric oxide production.

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Department of Free Radical Patophysiology, Institute of Biophysics, v. v. i., Academy of Sciences of the Czech Republic, and International Clinical Research Center-Center of Biomolecular and Cellular Engineering, St. Anne's University Hospital Brno, Kralovopolska 135, Brno, Czech Republic.


Endothelial dysfunction characterized by decreased nitric oxide (NO) bioavailability is the first stage of coronary artery disease. It is known that one of the factors associated with an increased risk of coronary artery disease is a high plasma level of uric acid. However, causative associations between hyperuricaemia and cardiovascular risk have not been definitely proved. In this work, we tested the effect of uric acid on endothelial NO bioavailability. Electrochemical measurement of NO production in acetylcholine-stimulated human umbilical endothelial cells (HUVECs) revealed that uric acid markedly decreases NO release. This finding was confirmed by organ bath experiments on mouse aortic segments. Uric acid dose-dependently reduced endothelium-dependent vasorelaxation. To reveal the mechanism of decreasing NO bioavailability we tested the effect of uric acid on reactive oxygen species production by HUVECs, on arginase activity, and on acetylcholine-induced endothelial NO synthase phosphorylation. It was found that uric acid increases arginase activity and reduces endothelial NO synthase phosphorylation. Interestingly, uric acid significantly increased intracellular superoxide formation. In conclusion, uric acid decreases NO bioavailability by means of multiple mechanisms. This finding supports the idea of a causal association between hyperuricaemia and cardiovascular risk.

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