Abstract
BackgroundSodium glucose co-transporter 2 inhibitor (SGLT2i), a new class of anti-diabetic drugs acting on inhibiting glucose resorption by kidneys, is shown beneficial in reduction of heart failure hospitalization and cardiovascular mortality. The mechanisms remain unclear. We hypothesized that SGLT2i, empagliflozin can improve cardiac hemodynamics in non-diabetic hypertensive heart failure.Methods and resultsThe hypertensive heart failure model had been created by feeding spontaneous hypertensive rats (SHR) with high fat diet for 32 weeks (total n = 13). Half SHRs were randomized to be administered with SGLT2i, empagliflozin at 20 mg/kg/day for 12 weeks. After evaluation of electrocardiography and echocardiography, invasive hemodynamic study was performed and followed by blood sample collection and tissue analyses. Empagliflozin exhibited cardiac (improved atrial and ventricular remodeling) and renal protection, while plasma glucose level was not affected. Empagliflozin normalized both end-systolic and end-diastolic volume in SHR, in parallel with parameters in echocardiographic evaluation. Empagliflozin also normalized systolic dysfunction, in terms of the reduced maximal velocity of pressure incline and the slope of end-systolic pressure volume relationship in SHR. In histological analysis, empagliflozin significantly attenuated cardiac fibrosis in both atrial and ventricular tissues. The upregulation of atrial and ventricular expression of PPARα, ACADM, natriuretic peptides (NPPA and NPPB), and TNF-α in SHR, was all restored by treatment of empagliflozin.ConclusionsEmpagliflozin improves hemodynamics in our hypertensive heart failure rat model, associated with renal protection, attenuated cardiac fibrosis, and normalization of HF genes. Our results contribute some understanding of the pleiotropic effects of empagliflozin on improving heart function.
Highlights
Sodium glucose co-transporter 2 inhibitors (SGLT2i) are a new class of anti-diabetic drugs acting on inhibiting glucose and sodium resorption by the kidneys
We previously reported that high-fat diet induced adverse atrial and ventricular remodeling in old rats with spontaneous hypertension, through upregulation of PPARα, ACADM and TNF-α, and a strong upregulation of α-MHC in atria and ventricles [14]
The principal comparisons are of spontaneous hypertensive rats (SHR) who received no EMPA treatment and SHR who received EMPA
Summary
Sodium glucose co-transporter 2 inhibitors (SGLT2i) are a new class of anti-diabetic drugs acting on inhibiting glucose and sodium resorption by the kidneys. For diabetes patients with systolic heart failure, ongoing clinical trials are performed to evaluate the cardiovascular effects of SGLT2i in pre-diabetes [5, 6]. There are emerging evidences for a diabetic independence that SGLT2i can be beneficial to non-diabetes patients with HF. Sodium glucose co-transporter 2 inhibitor (SGLT2i), a new class of anti-diabetic drugs acting on inhibit‐ ing glucose resorption by kidneys, is shown beneficial in reduction of heart failure hospitalization and cardiovascular mortality. We hypothesized that SGLT2i, empagliflozin can improve cardiac hemody‐ namics in non-diabetic hypertensive heart failure
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