ArticleAmerican journal of physiology. Heart and circulatory physiology2011
Hypertension from chronic central sodium chloride in mice is mediated by the ouabain-binding site on the Na,K-ATPase α₂-isoform.
Article in American journal of physiology. Heart and circulatory physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Sensational site: the sodium pump ouabain-binding site and its ligands.American journal of physiology. Cell physiology · 2024Review
- Stroke-prone salt-sensitive spontaneously hypertensive rats show higher susceptibility to spreading depolarization (SD) and altered hemodynamic responses to SD.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Does gender influence cardiovascular remodeling in C57BL/6J mice fed a high-fat, high-sucrose and high-salt diet?International journal of experimental pathology · 2019Review
- Central and peripheral slow-pressor mechanisms contributing to Angiotensin II-salt hypertension in rats.Cardiovascular research · 2018Article
- 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
- Salt Sensitivity: Challenging and Controversial Phenotype of Primary Hypertension.Current hypertension reports · 2016Review
- How Does Circadian Rhythm Impact Salt Sensitivity of Blood Pressure in Mice? A Study in Two Close C57Bl/6 Substrains.PloS one · 2016Article
- Enhanced expression of epithelial sodium channels causes salt-induced hypertension in mice through inhibition of the α2-isoform of Na+, K+-ATPase.Physiological reports · 2015Article
- Na+/Ca2+ exchange and Na+/K+-ATPase in the heart.The Journal of physiology · 2015Review
- Knockout of the Na,K-ATPase α2-isoform in cardiac myocytes delays pressure overload-induced cardiac dysfunction.American journal of physiology. Heart and circulatory physiology · 2013Article
- Alternating hemiplegia of childhood-related neural and behavioural phenotypes in Na+,K+-ATPase α3 missense mutant mice.PloS one · 2013Article
- Salt sensitivity, endogenous ouabain and hypertension.Current opinion in nephrology and hypertension · 2013Review
- How NaCl raises blood pressure: a new paradigm for the pathogenesis of salt-dependent hypertension.American journal of physiology. Heart and circulatory physiology · 2012Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
A chronic increase in the concentration of sodium chloride in the cerebrospinal fluid (CSF) (↑CSF [NaCl]) appears to be critically important for the development of salt-dependent hypertension. In agreement with this concept, increasing CSF [NaCl] chronically by intracerebroventricular (icv) infusion of NaCl-rich artificial CSF (aCSF-HiNaCl) in rats produces hypertension by the same mechanisms (i.e., aldosterone-ouabain pathway in the brain) as that produced by dietary sodium in salt-sensitive strains. We first demonstrate here that icv aCSF-HiNaCl for 10 days also causes hypertension in wild-type (WT) mice. We then used both WT and gene-targeted mice to explore the mechanisms. In WT mice with a ouabain-sensitive Na,K-ATPase α(2)-isoform (α2(S/S)), mean arterial pressure rose by ~25 mmHg within 2 days of starting aCSF-HiNaCl (0.6 nmol Na/min) and remained elevated throughout the study. Ouabain (171 pmol/day icv) increased blood pressure to a similar extent. aCSF-HiNaCl or ouabain given at the same rates subcutaneously instead of intracerebroventricularly had no effect on blood pressure. The pressor response to icv aCSF-HiNaCl was abolished by an anti-ouabain antibody given intracerebroventricularly but not subcutaneously, indicating that it is mediated by an endogenous ouabain-like substance in the brain. We compared the effects of icv aCSF-HiNaCl or icv ouabain on blood pressure in α2(S/S) versus knockout/knockin mice with a ouabain-resistant endogenous α(2)-subunit (α2(R/R)). In α2(R/R), there was no pressor response to icv aCSF-HiNaCl in contrast to WT mice. The α2(R/R) genotype also lacked a pressor response to icv ouabain. These data demonstrate that chronic ↑CSF [NaCl] causes hypertension in mice and that the blood pressure response is mediated by the ouabain-like substance in the brain, specifically by its binding to the α(2)-isoform of the Na,K-ATPase.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.