ArticleHypertension (Dallas, Tex. : 1979)2012
Salt-induced hypertension in a mouse model of Liddle syndrome is mediated by epithelial sodium channels in the brain.
Article in Hypertension (Dallas, Tex. : 1979), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 77 citations in OpenAlex.
- Elevated cerebrospinal fluid sodium in hypertensive human subjects with a family history of Alzheimer's disease.Physiological genomics · 2020Trial
- Differential Assembly of Native Epithelial Sodium Channel Complexes Across Mouse Epithelial Tissues.Kidney360 · 2026Article
- Differential Assembly of Native ENaC Complexes Across Mouse Epithelial Tissues.bioRxiv : the preprint server for biology · 2026Article
- Central nervous system mechanisms of salt-sensitive hypertension.Physiological reviews · 2025Review
- UBR1 Promotes Sex-Dependent ACE2 Ubiquitination in Hypertension.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Mechanisms of cerebrospinal fluid secretion by the choroid plexus epithelium: Application to various intracranial pathologies.Clinical anatomy (New York, N.Y.) · 2025Review
- Randomized Trial Comparing SGLT2 Inhibition and Hydrochlorothiazide on Sympathetic Traffic in Type 2 Diabetes.Kidney international reports · 2023Article
- Nedd4-2 up-regulation is associated with ACE2 ubiquitination in hypertension.Cardiovascular research · 2023Article
- Salt-dependent hypertension and inflammation: targeting the gut-brain axis and the immune system with Brazilian green propolis.Inflammopharmacology · 2020Review
- Cofilin participates in regulating alpha-epithelial sodium channel by interaction with 14-3-3 isoforms.Journal of biomedical research · 2020Article
- Dietary sodium modulates nephropathy in Nedd4-2-deficient mice.Cell death and differentiation · 2020Article
- Regulation of CSF and Brain Tissue Sodium Levels by the Blood-CSF and Blood-Brain Barriers During Migraine.Frontiers in computational neuroscience · 2020Article
- Deletion of the microRNA-degrading nuclease, translin/trax, prevents pathogenic vascular stiffness.American journal of physiology. Heart and circulatory physiology · 2019Article
- Changing views on the common physiologic abnormality that mediates salt sensitivity and initiation of salt-induced hypertension: Japanese research underpinning the vasodysfunction theory of salt sensitivity.Hypertension research : official journal of the Japanese Society of Hypertension · 2019Review
- Dietary salt blunts vasodilation by stimulating epithelial sodium channels in endothelial cells from salt-sensitive Dahl rats.British journal of pharmacology · 2018Article
- Liddle Syndrome: Review of the Literature and Description of a New Case.International journal of molecular sciences · 2018Review
- WW domain-binding protein 2 acts as an oncogene by modulating the activity of the glycolytic enzyme ENO1 in glioma.Cell death & disease · 2018Article
- Ion Channels in the Paraventricular Hypothalamic Nucleus (PVN); Emerging Diversity and Functional Roles.Frontiers in physiology · 2018Review
- Chronic high-sodium diet intake after weaning lead to neurogenic hypertension in adult Wistar rats.Scientific reports · 2017Article
- Understanding the Two Faces of Low-Salt Intake.Current hypertension reports · 2017Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
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.
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