ArticleHypertension research : official journal of the Japanese Society of Hypertension2019
Effects of empagliflozin on nondiabetic salt-sensitive hypertension in uninephrectomized rats.
Article in Hypertension research : official journal of the Japanese Society of Hypertension, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Impact of canagliflozin on the cardiorenal effects of dietary sodium intake in type 2 diabetes: a post hoc analysis of the CREDENCE trial.Diabetologia · 2026Trial
- SGLT2 inhibitors reduce the salt sensitivity of blood pressure in type 2 diabetes via enhanced postprandial natriuresis.Cardiovascular diabetology · 2026Trial
- How do SGLT2 inhibitors protect the kidney? A mediation analysis of the EMPA-REG OUTCOME trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Trial
- Organ-Specific Efficacy of Postischemic Empagliflozin in Acute Stroke and Myocardial Infarction Using Preclinical Models.Journal of the American Heart Association · 2026Article
- Protective effects of buloxibutid and empagliflozin on hypertension-induced cardiac and vascular injury in rats.Journal of molecular histology · 2026Article
- Article
- Empagliflozin demonstrates neuroprotective and cardioprotective effects by reducing ischemia/reperfusion damage in rat models of ischemic stroke and myocardial infarction.Scientific reports · 2025Article
- Effects of Dapagliflozin on Myocardial Gene Expression in BTBR Mice with Type 2 Diabetes.Cardiovascular drugs and therapy · 2025Article
- Oxidative Stress in Kidney Injury and Hypertension.Antioxidants (Basel, Switzerland) · 2024Review
- The potential anti-arrhythmic effect of SGLT2 inhibitors.Cardiovascular diabetology · 2024Review
- Gliflozins in the Treatment of Non-diabetic Experimental Cardiovascular Diseases.Physiological research · 2024Review
- Sodium Glucose Cotransporter-2 Inhibitors in Non-Diabetic Kidney Disease: Evidence in Experimental Models.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Sodium-Glucose Co-Transporter 2 Inhibitors: Mechanism of Action and Efficacy in Non-Diabetic Kidney Disease from Bench to Bed-Side.Journal of clinical medicine · 2024Review
- Associations of SGLT2 genetic polymorphisms with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Article
- Renoprotective effects of empagliflozin are linked to activation of the tubuloglomerular feedback mechanism and blunting of the complement system.American journal of physiology. Cell physiology · 2023Article
- Empagliflozin Protects against Haloperidol Experimentally-Induced Ovarian Toxicity.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Empagliflozin Is Not Renoprotective in Non-Diabetic Rat Models of Chronic Kidney Disease.Biomedicines · 2022Article
- Sodium-Glucose Cotransporter 2 Inhibitors and Cardiac Remodeling.Journal of cardiovascular translational research · 2022Review
- New insights and advances of sodium-glucose cotransporter 2 inhibitors in heart failure.Frontiers in cardiovascular medicine · 2022Review
- Renal outcomes with sodium-glucose cotransporters 2 inhibitors.Frontiers in endocrinology · 2022Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Impaired pressure natriuresis (PN) underlies salt-sensitive hypertension, and renal inflammation and hypoxia-inducible factor-1 (HIF-1) have been implicated in the modulation of systemic hypertension. Although sodium-glucose cotransporter-2 (SGLT2) inhibitors were reported to lower blood pressure (BP) in type 2 diabetes mellitus, whether they have a role in nondiabetic hypertensive kidney diseases is unclear. The present study was undertaken to investigate whether nondiabetic salt-sensitive hypertension and accompanying renal inflammation are ameliorated by SGLT2 inhibition. Male Sprague-Dawley rats were randomly divided into three groups: sham controls (SCs), uninephrectomized controls (UCs), and empagliflozin-treated rats (ETs). All rats were fed a rodent diet with 8% NaCl throughout the study period. Empagliflozin was orally administered for 3 weeks after uninephrectomy. Systolic blood pressure was recorded weekly, and kidneys were harvested for immunoblotting, immunohistochemistry, and quantitative PCR analysis at the end of the animal experiment. Systolic BP was significantly decreased in ETs that were orally given empagliflozin for 3 weeks after uninephrectomy. Although ETs did not show any increase in weekly measured urine sodium, the right-shifted PN relationship in UCs was improved by empagliflozin treatment. The expression of HIF-1α was increased in the renal outer medulla of ETs. Consistent with this, HIF prolyl-hydroxylase-2 protein and mRNA were decreased in ETs. The abundance of CD3 and ED-1 immunostaining in UCs was reduced by empagliflozin treatment. The increased IL-1ß, gp91phox, and NOX4 mRNA levels in UCs were also reversed. Empagliflozin restored impaired PN in nondiabetic hypertensive kidney disease in association with increased renal medullary expression of HIF-1α and amelioration of renal inflammation.
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