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

PAPEŽÍKOVÁ, Ivana; Michaela PEKAROVÁ; Hana KOLÁŘOVÁ; A KLINKE; D LAU; S BALDUS; Antonín LOJEK a Lukáš KUBALA. Uric acid modulates vascular endothelial function through the down regulation of nitric oxide production. Free Radical Res. Gordon and Breach, 2013. ISSN 1071-5762. Dostupné z: https://doi.org/10.3109/10715762.2012.747677.

Základní údaje

Originální název

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

Název česky

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

Název anglicky

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

Autoři

PAPEŽÍKOVÁ, Ivana; Michaela PEKAROVÁ; Hana KOLÁŘOVÁ; A KLINKE; D LAU; S BALDUS; Antonín LOJEK a Lukáš KUBALA

Vydání

Free Radical Res. Gordon and Breach, 2013, 1071-5762

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Další údaje

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.989

Označené pro přenos do RIV

Ne

DOI

https://doi.org/10.3109/10715762.2012.747677

Klíčová slova česky

hyperuricaemia, endothelial dysfunction, coronary artery disease, nitric oxide, endothelial nitric oxide synthase, reactive oxygen species, arginase activity

Klíčová slova anglicky

hyperuricaemia, endothelial dysfunction, coronary artery disease, nitric oxide, endothelial nitric oxide synthase, reactive oxygen species, arginase activity

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Anotace

V originále

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.

Česky

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.

Anglicky

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.