Empagliflozin as a Method for Correcting Endothelial Dysfunction in Rats Fed a High-Fat Diet

Changes in the qualitative and quantitative composition of the human diet have currently led to a significant increase in the incidence of obesity and diabetes mellitus, so the search for methods to correct metabolic disorders caused by excessive fat intake is an urgent task. The aim of this study was to test the hypothesis that empagliflozin (EMPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, may have a protective effect on the reactivity of rat mesenteric arteries under a high-fat alimentary load. HFD group rats (n = 15) fed a diet containing 50% animal fat for 10 weeks. EMPA group animals (n = 12) fed the same HFD but supplemented with 1 mg/kg EMPA daily. The control group comprised SD rats (n = 15), which received a standard diet (SD) with normal fat content (15%). Using photo- and video recording of mesenteric arteries, changes in the diameter of phenylephrine-preconstricted vessels were assessed in response to acetylcholine (ACh) and sodium nitroprusside (SNP), as well as phenylephrine, application. It was shown that on an HFD, EMPA prevented such HFD-associated abnormalities as blood pressure elevation, visceral obesity, increased triglyceride and LDL cholesterol levels, and enhanced insulin resistance. EMPA also reduced HFD-associated endothelial dysfunction, with the amplitude of vasodilation in response to ACh being higher in EMPA-treated than in HFD-fed rats (96.8 ± 2.9 and 85.0 ± 2.6%, respectively), while remaining lower than in the control group (106.1 ± 3.2%). EMPA did not alter vasoreactivity to SNP, as the dilation amplitude was similar across all studied groups. Thus, the use of EMPA reduced the severity of HFD-associated dyslipidemia and also alleviated endothelial dysfunction by preserving endothelium-derived NO production.