No development of hypertension in the hyperuricemic liver-Glut9 knockout mouse.

Détails

ID Serval
serval:BIB_ADDFD3771EC7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
No development of hypertension in the hyperuricemic liver-Glut9 knockout mouse.
Périodique
Kidney International
Auteur(s)
Preitner F., Pimentel A., Metref S., Berthonneche C., Sarre A., Moret C., Rotman S., Centeno G., Firsov D., Thorens B.
ISSN
1523-1755 (Electronic)
ISSN-L
0085-2538
Statut éditorial
Publié
Date de publication
2015
Volume
87
Numéro
5
Pages
940-947
Langue
anglais
Résumé
Urate is the metabolic end point of purines in humans. Although supra-physiological plasma urate levels are associated with obesity, insulin resistance, dyslipidemia, and hypertension, a causative role is debated. We previously established a mouse model of hyperuricemia by liver-specific deletion of Glut9, a urate transporter that provides urate to the hepatocyte enzyme uricase. These LG9 knockout mice show mild hyperuricemia (120 μmol/l), which can be further increased by the urate precursor inosine. Here, we explored the role of progressive hyperuricemia on the cardiovascular function. Arterial blood pressure and heart rate were periodically measured by telemetry over 6 months in LG9 knockout mice supplemented with incremental amounts of inosine in a normal chow diet. This long-term inosine treatment elicited a progressive increase in uricemia up to 300 μmol/l; however, it did not modify heart rate or mean arterial blood pressure in LG9 knockout compared with control mice. Inosine treatment did not alter cardiac morphology or function measured by ultrasound echocardiography. However, it did induce mild renal dysfunction as revealed by higher plasma creatinine levels, lower glomerular filtration rate, and histological signs of chronic inflammation and fibrosis. Thus, in LG9 knockout mice, inosine-induced hyperuricemia was not associated with hypertension despite partial renal deficiency. This does not support a direct role of urate in the control of blood pressure.
Pubmed
Web of science
Création de la notice
09/01/2015 15:01
Dernière modification de la notice
20/08/2019 15:17
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