ArticleJournal of the American Heart Association2022
Sodium-Glucose Cotransporter 2 Inhibitor Canagliflozin Antagonizes Salt-Sensitive Hypertension Through Modifying Transient Receptor Potential Channels 3 Mediated Vascular Calcium Handling.
Article in Journal of the American Heart Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Cardiorenal Associations in Preclinical Modeling: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2026Pooled it
- SGLT2 inhibitor ameliorates hypertension by regulating the CYP4A/20-HETE pathway in the kidney.Bioscience reports · 2026Article
- The role of arachidonic acid metabolites in the subtype classification and pathogenesis of primary aldosteronism.iScience · 2026Article
- Prognostic Stratification and Subtyping of Glioblastoma Using Transient Receptor Potential Channels.Human mutation · 2026Article
- Sodium-glucose cotransporter 2 inhibitors for hypertension in cardiovascular-kidney-metabolic syndrome.Experimental physiology · 2025Review
- Optimizing Nephron Performance: The Old, the New, and the New-Old Diuretic Therapies.Biomedicines · 2025Review
- Sodium-glucose exchanger 2 inhibitor canagliflozin promotes mitochondrial metabolism and alleviates salt-induced cardiac hypertrophy via preserving SIRT3 expression.Journal of advanced research · 2025Article
- Article
- Role of transient receptor potential channels in the regulation of vascular tone.Drug discovery today · 2024Review
- Canagliflozin and irbesartan ameliorate renal fibrosis via the TGF-β1/Smad signaling pathway in Dahl salt-sensitive rats.The Journal of international medical research · 2023Article
- Combined analysis of the proteome and metabolome provides insight into microRNA-1174 function in Aedes aegypti mosquitoes.Parasites & vectors · 2023Article
- Empagliflozin suppressed cardiac fibrogenesis through sodium-hydrogen exchanger inhibition and modulation of the calcium homeostasis.Cardiovascular diabetology · 2023Article
- The role of SGLT2i in attenuating residual cardiovascular risk through blood pressure-lowering: mechanistic insights and perspectives.Frontiers in clinical diabetes and healthcare · 2023Review
- SGLT2 Inhibitors-A Medical Revelation: Molecular Signaling of Canagliflozin Underlying Hypertension and Vascular Remodeling.Journal of the American Heart Association · 2022Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background Salt-sensitive hypertension is highly prevalent and associated with cardiorenal damage. Large clinical trials have demonstrated that SGLT2 (sodium-glucose cotransporter 2) inhibitors exert hypotensive effect and cardiorenal protective benefits in patients with hypertension with and without diabetes. However, the underlying mechanism remains elusive. Methods and Results Dahl salt-sensitive rats and salt-insensitive controls were fed with 8% high-salt diet and some of them were treated with canagliflozin. The blood pressure, urinary sodium excretion, and vascular function were detected. Transient receptor potential channel 3 (TRPC3) knockout mice were used to explain the mechanism. Canagliflozin treatment significantly reduced high-salt-induced hypertension and this effect was not totally dependent on urinary sodium excretion in salt-sensitive hypertensive rats. Assay of vascular function and proteomics showed that canagliflozin significantly inhibited vascular cytoplasmic calcium increase and vasoconstriction in response to high-salt diet. High salt intake increased vascular expression of TRPC3 in salt-sensitive rats, which could be alleviated by canagliflozin treatment. Overexpression of TRPC3 mimicked salt-induced vascular cytosolic calcium increase in vitro and knockout of TRPC3 erased the antihypertensive effect of canagliflozin. Mechanistically, high-salt-induced activation of NCX1 (sodium-calcium exchanger 1) reverse mode increased cytoplasmic calcium level and vasoconstriction, which required TRPC3, and this process could be blocked by canagliflozin. Conclusions We define a previously unrecognized role of TRPC3/NCX1 mediated vascular calcium dysfunction in the development of high-salt-induced hypertension, which can be improved by canagliflozin treatment. This pathway is potentially a novel therapeutic target to antagonize salt-sensitive hypertension.
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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.