ArticleCirculation. Heart failure2021
Enhanced Expression and Function of Renal SGLT2 (Sodium-Glucose Cotransporter 2) in Heart Failure: Role of Renal Nerves.
Article in Circulation. Heart failure, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Cardiorenal Associations in Preclinical Modeling: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2026Pooled it
- Short- and mid-term effects of empagliflozin on sodium balance and fluid regulation in chronic heart failure.European journal of heart failure · 2025Trial
- Pulmonary congestion relief by adding dapagliflozin to intravenous loop diuretic in acute heart failure patients.ESC heart failure · 2025Trial
- Neural Upregulation of SGLT2-MAP17-PDZK1 Complex in Kidneys of Rats With Heart Failure.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Autonomic control of the vasculature in CKD: leveraging renal denervation.Frontiers in neuroscience · 2026Review
- SGLT2 inhibitors for the prevention and treatment of heart failure: A scientific statement of the HFA and the HFAI.ESC heart failure · 2025Review
- When the Heart Hurts the Kidneys: From Flow to Translational Future.Seminars in nephrology · 2025Review
- Diuretic Use in Heart Failure.Reviews in cardiovascular medicine · 2025Review
- Interaction between SGLT2 and the sympathetic nervous system in normal and various cardiovascular metabolic disease states.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Review
- Renal denervation in the setting of heart failure.Heart failure reviews · 2025Review
- Sodium-glucose co-transporter 2 inhibitors: Prospects for canine myxomatous mitral valve disease and finding the "right drug" and the "right dose" for dogs.The Journal of veterinary medical science · 2025Review
- Neuro-immune axis in atherosclerosis: mechanisms of regulation and therapeutic opportunities.Frontiers in immunology · 2025Review
- Pharmacological Interventions for Cirrhotic Ascites: From Challenges to Emerging Therapeutic Horizons.Gut and liver · 2024Review
- Effects of renal denervation on the incidence and severity of cardiovascular diseases.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- Unraveling the Cardiac Matrix: From Diabetes to Heart Failure, Exploring Pathways and Potential Medications.Biomedicines · 2024Review
- Unravelling the effect of renal denervation on glucose homeostasis: more questions than answers?Acta diabetologica · 2024Review
- Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction.Journal of the American Heart Association · 2024Article
- Immunomodulation and immunopharmacology in heart failure.Nature reviews. Cardiology · 2024Review
- Effect of Empagliflozin Treatment on Ventricular Repolarization Parameters.Reviews in cardiovascular medicine · 2024Article
- Impact of Dapagliflozin on the Renal Function and Damage in Patients with Heart Failure with a Reduced Ejection Fraction.Internal medicine (Tokyo, Japan) · 2024Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRecent clinical studies demonstrate that SGLT2 (sodium-glucose cotransporter 2) inhibitors ameliorate heart failure (HF). The present study was conducted to assess the expression and function of renal SGLT2 and the influence of enhanced renal sympathetic tone in HF.
methodsFour weeks after coronary artery ligation surgery to induce HF, surgical bilateral renal denervation (RDN) was performed in rats. Four groups of rats (Sham-operated control [Sham], Sham+RDN, HF and HF+RDN; n=6/group) were used. Immunohistochemistry and Western blot analysis were performed to evaluate the renal SGLT2 expression. One week after RDN (5 weeks after induction of HF), intravenous injection of SGLT2 inhibitor dapagliflozin were performed to assess renal excretory responses. In vitro, human embryonic kidney cells were used to investigate the fractionation of SGLT2 after norepinephrine treatment.
resultsIn rats with HF, (1) SGLT2 expression in the proximal tubule of the kidney was increased; (2) the response of increases in urine flow, sodium excretion, and glucose excretion to dapagliflozin were greater; and (3) RDN attenuated renal SGLT2 expression and normalized renal functional responses to dapagliflozin. In vitro, norepinephrine promoted translocation of SGLT2 to the cell membrane.
conclusionsThese results indicate that the enhanced tonic renal sympathetic nerve activation in HF increases the expression and functional activity of renal SGLT2. Potentiated trafficking of SGLT2 to cell surface in renal proximal tubules mediated by norepinephrine may contribute to this functional activation of SGLT2 in HF. These findings provide critical insight into the underlying mechanisms for the beneficial effects of SGLT2 inhibitors on HF reported in the clinical studies.
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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.