Abstract
Empagliflozin (EMPA), a selective SGLT2 inhibitor, significantly reduced cardiovascular mortality and hospitalization for heart failure in patients with type 2 diabetes at high cardiovascular risk, but the protective mechanisms remain unclear. This study evaluates the effect of EMPA on the endothelial function, and the heart structure and function in an experimental model of metabolic syndrome with HFpEF, the ZSF1 rat, and its lean control (Ctrl). Rats received either the control diet or the diet containing EMPA (30mg/kg/day) for 6 weeks. Vascular reactivity was assessed in the mesenteric artery using organ chambers, and the heart function and structural changes by echocardiography. In the mesenteric artery, acetylcholine (ACh)-induced endothelium-dependent relaxations were slightly but significantly reduced and endothelium-dependent contractile responses (EDCFs) increased in ZSF1 compared to Ctrl rats. The cyclooxygenase inhibitor indomethacin improved relaxations and abolished EDCFs to ACh in ZSF1 rats. The 6-week EMPA treatment improved the relaxation and blunted EDCFs to ACh in the ZSF1. The weight of the heart and of each part, and the left ventricle area were increased in the ZSF1, and significantly reduced by the EMPA treatment, except for left auricle plus septum weight, which did not reach significance. Left ventricle ejection fraction and cardiac output were similar in all groups. The EMPA treatment reduced the increased body weight and that of lungs, spleen, liver and perirenal fat, and hyperglycemia, and increased blood ketone levels and urinary glucose excretion in ZSF1 rats. The EMPA treatment improved body weight, hyperglycemia, and both endothelial function and cardiac remodeling in the metabolic syndrome with HFpEF ZSF1 rat. The protective vascular effect involves improved endothelium-dependent relaxations and blunted EDCFs most likely by targeting the cyclooxygenase pathway.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.