Effect of Empagliflozin on the Functional State of Skin Microcirculatory Vessels in Wistar Rats with Kidney Dysfunction

The aim of the study was to test the hypothesis of a possible protective effect of empagliflozin, an SGLT2 blocker, on the functional state of skin microvessels in a rat early-stage chronic kidney disease (CKD) model. In the NE group rats (n = 10), kidney dysfunction was induced by a combination of 3/4 nephrectomy and a high-sodium dietary load (4% NaCl); animals in the EMPA group (n = 10), after CKD modeling, received 1 mg/kg of empagliflozin; control rats in the SO group (n = 10) underwent a sham operation and fed a standard diet with normal salt content. Baseline skin microcirculation parameters and their changes in response to acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed using laser Doppler flowmetry; skin microvascular tone was calculated by a wavelet analysis. It was shown that in CKD, EMPA had no effect on the levels of arterial pressure and uremia, as well as the mean skin microcirculation index (MCI). At the same time, EMPA prevented a nephrectomy-specific increase in microvascular tone in the endothelial, neurogenic, and myogenic ranges. ACh iontophoresis increased the MCI by 59.4 ± 4.4% in the EMPA group, by 38.0 ± 8.3% in the NE group, and by 60.6 ± 5.7% in the SO group, while SNP increased it by 53.0 ± 3.5%, 36.4 ± 6.0%, and 68.5 ± 8.7%, respectively. Thus, EMPA prevented the enhancement of tonic influences on the skin microcirculatory vessels in the studied ranges, as well as the development of microvascular endothelial dysfunction, in a rat early-stage CKD model, preserving the vascular reactivity of the skin microcirculatory bed to vasodilator agents at the level of control animals.