Journal article
Salt-induced hypertension in a mouse model of Liddle syndrome is mediated by epithelial sodium channels in the brain
Hypertension, Vol.58(5), pp.E58-E59
11/01/2011
DOI: 10.1161/HYPERTENSIONAHA.112.193045
PMCID: PMC3514876
PMID: 22802227
Abstract
Neural precursor cell expressed and developmentally downregulated 4-2 protein (Nedd4-2) facilitates the endocytosis of epithelial Na channels (ENaCs). Both mice and humans with a loss of regulation of ENaC by Nedd4-2 have salt-induced hypertension. ENaC is also expressed in the brain, where it is critical for hypertension on a high-salt diet in salt-sensitive rats. In the present studies we assessed whether Nedd4-2 knockout (-/-) mice have the following: (1) increased brain ENaC; (2) elevated cerebrospinal fluid (CSF) sodium on a high-salt diet; and (3) enhanced pressor responses to CSF sodium and hypertension on a high-salt diet, both mediated by brain ENaC. Prominent choroid plexus and neuronal ENaC staining was present in -/- but not in wild-type mice. In chronically instrumented mice, ICV infusion of Na-rich artificial CSF increased mean arterial pressure 3-fold higher in -/- than in wild-type mice. ICV infusion of the ENaC blocker benzamil abolished this enhancement. In telemetered -/- mice on a high-salt diet (8% NaCl), CSF [Na(+)], mean arterial pressure, and heart rate increased significantly, mean arterial pressure by 30 to 35 mmHg. These mean arterial pressure and heart rate responses were largely prevented by ICV benzamil but only to a minor extent by SC benzamil at the ICV rate. We conclude that increased ENaC expression in the brain of Nedd4-2 -/- mice mediates their hypertensive response to a high-salt diet by causing increased sodium levels in the CSF, as well as hyperresponsiveness to CSF sodium. These findings highlight the possible causative contribution of central nervous system ENaC in the etiology of salt-induced hypertension.
Details
- Title: Subtitle
- Salt-induced hypertension in a mouse model of Liddle syndrome is mediated by epithelial sodium channels in the brain
- Creators
- James Van HuysseBaoli Yang - University of IowaFrans H. LeenenMd Shahrier Amin - University of Ottawa
- Resource Type
- Journal article
- Publication Details
- Hypertension, Vol.58(5), pp.E58-E59
- DOI
- 10.1161/HYPERTENSIONAHA.112.193045
- PMID
- 22802227
- PMCID
- PMC3514876
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Grant note
- Grant support P50 DK052617/DK/NIDDK NIH HHS/United States MOP 74432/Canadian Institutes of Health Research/Canada P50-DK52617/DK/NIDDK NIH HHS/United States
- Language
- English
- Date published
- 11/01/2011
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9983557604302771
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