ArticlePhysiological reports2015
Enhanced expression of epithelial sodium channels causes salt-induced hypertension in mice through inhibition of the α2-isoform of Na+, K+-ATPase.
Article in Physiological reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Sensational site: the sodium pump ouabain-binding site and its ligands.American journal of physiology. Cell physiology · 2024Review
- Salt Sensitivity of Blood Pressure in Blacks and Women: A Role of Inflammation, Oxidative Stress, and Epithelial NaAntioxidants & redox signaling · 2021Review
- Immune Mechanisms of Dietary Salt-Induced Hypertension and Kidney Disease: Harry Goldblatt Award for Early Career Investigators 2020.Hypertension (Dallas, Tex. : 1979) · 2021Review
- Salt-dependent hypertension and inflammation: targeting the gut-brain axis and the immune system with Brazilian green propolis.Inflammopharmacology · 2020Review
- Regulation of CSF and Brain Tissue Sodium Levels by the Blood-CSF and Blood-Brain Barriers During Migraine.Frontiers in computational neuroscience · 2020Article
- Epithelial NaAnnual review of physiology · 2018Review
- The pump, the exchanger, and the holy spirit: origins and 40-year evolution of ideas about the ouabain-NaAmerican journal of physiology. Cell physiology · 2018Review
- How does pressure overload cause cardiac hypertrophy and dysfunction? High-ouabain affinity cardiac NaAmerican journal of physiology. Heart and circulatory physiology · 2017Review
- Update on angiotensin II: new endocrine connections between the brain, adrenal glands and the cardiovascular system.Endocrine connections · 2017Review
- Pivotal role of α2 NaThe Journal of physiology · 2016Review
- Endogenous Ouabain: Recent Advances and Controversies.Hypertension (Dallas, Tex. : 1979) · 2016Review
- An isoform of Nedd4-2 is critically involved in the renal adaptation to high salt intake in mice.Scientific reports · 2016Article
- The Role of CNS in the Effects of Salt on Blood Pressure.Current hypertension reports · 2016Review
- Nontubular epithelial Na+ channel proteins in cardiovascular regulation.Physiological reports · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Knockout of the Nedd4-2 gene in mice results in overexpression of epithelial sodium channels (ENaC) on the plasma membrane in the kidney, choroid plexus and brain nuclei. These mice exhibit enhanced pressor responses to CSF [Na(+)] as well as dietary salt-induced hypertension which both can be blocked by central infusion of the ENaC blocker benzamil. Functional studies suggest that ENaC activation in the CNS results in release of endogenous ouabain (EO) and inhibition of the α2-isoform of Na(+), K(+)-ATPase. To test this concept more specifically, we studied Nedd4-2(-/-) mice expressing the ouabain-resistant α2R/R-isoform of Na(+), K(+)-ATPase. Intracerebroventricular (icv) infusion of Na(+)-rich aCSF (225 mmol/L Na(+) at 0.4 μL/min) increased MAP by 10-15 mmHg in wild-type mice and by 25-30 mmHg in Nedd4-2(-/-) mice, but by only ~5 mmHg in α2R/R and in α2R/R/Nedd4-2(-/-) mice. Icv infusion of EO-binding Fab fragments also blocked the BP response in Nedd4-2(-/-) mice. In Nedd4-2(-/-) mice, 8% high-salt diet increased MAP by 25-30 mmHg, but in α2R/R/Nedd4-2(-/-) mice, it increased by only 5-10 mmHg. In contrast, Nedd4-2(-/-) or α2R/R did not affect the hypertension caused by sc infusion of Ang II. These findings substantiate the concept that enhanced ENaC activity causes salt-induced pressor responses mainly through EO inhibiting the α2-isoform of Na(+), K(+)-ATPase in the brain.
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