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Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis.
- Source :
- FASEB Journal; Jul2014, Vol. 28 Issue 7, p3197-3204, 8p
- Publication Year :
- 2014
-
Abstract
- Endothelial dysfunction is defined as impairment of the balance between endothelium-dependent vasodilation and constriction. Despite evidence ofuric acid-induced endothelial dysfunction, a relationship with insulin resistance has not been clearly established. In this study, we investigated the role of vascular insulin resistance in uric acid-induced endothelial dysfunction. Uric acid inhibited insulin-induced endothelial nitric oxide synthase (eNOS) phosphorylation and NO production more substantially than endothelin-1 expression in HUVECs, with IC<subscript>50</subscript> of 51.0, 73.6, and 184.2, respectively. Suppression of eNOS phosphorylation and NO production by uric acid was PI3K/Akt-dependent, as verified by the transfection with p110. Treatment of rats with the uricase inhibitor allantoxanamide induced mild hyperuricemia and increased mean arterial pressure by 25%. While hyperuricemic rats did not show systemic insulin resistance, they showed impaired vasorelaxation induced by insulin by 56%. A compromised insulin response in terms of the Akt/eNOS pathway was observed in the aortic ring of hyperuricemic rats. Coadministration with allopurinol reduced serum uric acid levels and blood pressure and restored the effect of insulin on Akt-eNOS pathway and vasorelaxation. Taken together, uric acid induced endothelial dysfunction by contributing to vascular insulin resistance in terms of insulin-induced NO production, potentially leading to the development of hypertension. [ABSTRACT FROM AUTHOR]
- Subjects :
- ENDOTHELIUM
VASODILATION
INSULIN research
NITRIC oxide
PHOSPHORYLATION
Subjects
Details
- Language :
- English
- ISSN :
- 08926638
- Volume :
- 28
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- FASEB Journal
- Publication Type :
- Academic Journal
- Accession number :
- 96991582
- Full Text :
- https://doi.org/10.1096/fj.13-247148