ReviewHypertension research : official journal of the Japanese Society of Hypertension2011
The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin-angiotensin-aldosterone system, oxidative stress and endogenous digitalis in the brain.
Review in Hypertension research : official journal of the Japanese Society of Hypertension, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 137 citations in OpenAlex.
- Differential Assembly of Native Epithelial Sodium Channel Complexes Across Mouse Epithelial Tissues.Kidney360 · 2026Article
- Neuro-renin-angiotensin-aldosterone system axis in alzheimer's disease: from molecular dysregulation to therapeutic redirection.Metabolic brain disease · 2026Review
- Differential Assembly of Native ENaC Complexes Across Mouse Epithelial Tissues.bioRxiv : the preprint server for biology · 2026Article
- Pathway-specific polygenic risk scores for blood pressure traits in a West African cohort.Frontiers in cardiovascular medicine · 2026Article
- From peripheral initiation to central integration: a narrative review of the antihypertensive mechanisms of acupuncture in regulating autonomic nervous system homeostasis.Frontiers in neuroscience · 2026Review
- Machine learning prediction of hypertension integrating polygenic risk scores in inner Eurasian populations.Frontiers in cardiovascular medicine · 2026Article
- A High-Fat Diet Increases Kidney Fibrosis Through Regulating TGF-β and PDGF-β Signaling Pathways in Normotensive and Hypertensive Rat Models.International journal of molecular sciences · 2025Article
- Review
- Genetic Polymorphisms and Genetic Risk Scores Contribute to the Risk of Coronary Artery Disease (CAD) in a North Indian Population.International journal of molecular sciences · 2024Article
- Usability of myocardial work parameters to demonstrate subclinical myocardial involvement in normotensive individuals with exaggerated hypertensive response in treadmill exercise testing.Journal of clinical hypertension (Greenwich, Conn.) · 2024Article
- Associations of Proteomics With Hypertension and Systolic Blood Pressure: KORA S4/F4/FF4 and KORA Age1/Age2 Cohort Studies.Hypertension (Dallas, Tex. : 1979) · 2024Article
- α-Mangostin reduces hypertension in spontaneously hypertensive rats and inhibits EMT and fibrosis in Ang II-induced HK-2 cells.International journal of medical sciences · 2024Article
- Risk factors of acute ischemic stroke and the role of angiotensin I in predicting prognosis of patients undergoing endovascular thrombectomy.Frontiers in endocrinology · 2024Article
- Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Hypertension Induces Pro-arrhythmic Cardiac Connexome Disorders: Protective Effects of Treatment.Biomolecules · 2023Review
- When blood pressure refuses to budge: exploring the complexity of resistant hypertension.Frontiers in cardiovascular medicine · 2023Review
- Structure Characterization and Antihypertensive Effect of an Antioxidant Peptide Purified from Alcalase Hydrolysate of Velvet Antler.Food science of animal resources · 2023Article
- Understanding diabetes-induced cardiomyopathy from the perspective of renin angiotensin aldosterone system.Pflugers Archiv : European journal of physiology · 2022Review
- Adherence to lifelines diet score and risk factors of metabolic syndrome among overweight and obese adults: A cross-sectional study.Frontiers in nutrition · 2022Article
- Hypertension in chronic kidney disease: What lies behind the scene.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The central nervous system has a key role in regulating the circulatory system by modulating the sympathetic and parasympathetic nervous systems, pituitary hormone release, and the baroreceptor reflex. Digoxin- and ouabain-like immunoreactive materials were found >20 years ago in the hypothalamic nuclei. These factors appeared to localize to the paraventricular and supraoptic nuclei and the nerve fibers at the circumventricular organs and supposed to affect electrolyte balance and blood pressure. The turnover rate of these materials increases with increasing sodium intake. As intracerebroventricular injection of ouabain increases blood pressure via sympathetic activation, an endogenous digitalis-like factor (EDLF) was thought to regulate cardiovascular system-related functions in the brain, particularly after sodium loading. Experiments conducted mainly in rats revealed that the mechanism of action of ouabain in the brain involves sodium ions, epithelial sodium channels (ENaCs) and the renin-angiotensin-aldosterone system (RAAS), all of which are affected by sodium loading. Rats fed a high-sodium diet develop elevated sodium levels in their cerebrospinal fluid, which activates ENaCs. Activated ENaCs and/or increased intracellular sodium in neurons activate the RAAS; this releases EDLF in the brain, activating the sympathetic nervous system. The RAAS promotes oxidative stress in the brain, further activating the RAAS and augmenting sympathetic outflow. Angiotensin II and aldosterone of peripheral origin act in the brain to activate this cascade, increasing sympathetic outflow and leading to hypertension. Thus, the brain Na(+)-ENaC-RAAS-EDLF axis activates sympathetic outflow and has a crucial role in essential and secondary hypertension. This report provides an overview of the central mechanism underlying hypertension and discusses the use of antihypertensive agents.
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Registered trials
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.