244-LB: The GABA Neurons in the Multiple Autonomic Areas of the Central Nervous System Mediate the Cardiovascular Regulation by SGLT-2 Inhibitors

Abstract

Purpose: This study investigates the possible effect and central mechanism of novel antidiabetic medication sodium glucose transporter-2 (SGLT-2i) on the cardiovascular activity. Material and methods: Thirty-four normal male C57BL/6 mice were randomly assigned to receive single Dapagliflozin (1.52mg/kg) dose via intragastric gavage or a comparable dose of saline. Glycemic level (BG), blood pressure (BP) and heart rate (HR) were measured 2 hours after administration of the respective treatments. Immunohistochemical tests were performed to determine the effect of SGLT-2i on neural localization of SGLT-2 and c-Fos. Results: Administration of SGLT-2i significantly decreased BP but did not affect the HR. There was no difference in BG between the two groups. Results showed that SGLT-2 was localized to specific regions involved in autonomic control. Expression of c-Fos was significantly higher in major critical nuclei in the aforementioned regions in groups treated with Dapagliflozin. Conclusion: This study demonstrates that SGLT-2 is expressed in CNS tissues involved in autonomic control and possibly influence cardiovascular function. Dapagliflozin influences central autonomic activity via unidentified pathways by inhibiting central or peripheral SGLT-2. These results provide a new concept that sympathetic inhibition by SGLT-2i can be mediated by central autonomic system, a mechanism that explains how SGLT-2i improves the cardiovascular function. Disclosure S. Wen: None. Funding Pudong New Area Health Planning Commission (PWZZK2017-03); Shanghai Municipal Health Planning Committee (ZHYY-ZXYJHZX-2-201712); National Natural Science Foundation of China (81370932, 21675034); Pudong Health Bureau of Shanghai (PWR12014-06); Outstanding Clinical Discipline Project of Shanghai Pudong (PWYgy-2018-08); Shanghai Natural Science Foundation (19ZR1447500)