SGLT2 Inhibitor-Induced Sympathoinhibition: A Novel Mechanism for Cardiorenal Protection

JACC. Basic to Translational Science
Lakshini HeratVance B Matthews

Abstract

Recent clinical trial data suggest a cardiorenal protective effect of sodium glucose cotransporter 2 (SGLT2) inhibition. We demonstrate that chemical denervation in neurogenic hypertensive Schlager (BPH/2J) mice reduced blood pressure, improved glucose homeostasis, and reduced renal SGLT2 protein expression. Inhibition of SGLT2 prevented weight gain, reduced blood pressure, significantly reduced elevations of tyrosine hydroxylase and norepinephrine, and protects against endothelial dysfunction. These findings provide evidence for significant crosstalk between activation of the sympathetic nervous system and SGLT2 regulation and possible ancillary effects on endothelial function, which may contribute to the observed cardiorenal protective effects of SGLT2 inhibition.

Citations

Apr 18, 2020·Expert Opinion on Pharmacotherapy·Lakshini Y HeratMarkus P Schlaich
Apr 21, 2020·American Journal of Hypertension·Waleed Ali, George L Bakris
Sep 15, 2020·Jornal brasileiro de nefrologia : ʹorgão oficial de Sociedades Brasileira e Latino-Americana de Nefrologia·Vikas S SridharDavid Z Cherney
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Sep 29, 2020·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Xi RongXiaoping Chen
Jul 21, 2020·World Journal of Gastroenterology : WJG·Lakshini Y HeratVance B Matthews
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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA

Software Mentioned

GraphPad Prism
Excel

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