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

Lakshini Y. Herat, Aaron L. Magno, Caroline Rudnicka, Jana Hricova, Revathy Carnagarin, Natalie C. Ward, Angelique Arcambal, Marcio G. Kiuchi, Geoff A. Head, Markus P. Schlaich, Vance B. Matthews

Research output: Contribution to journalArticlepeer-review

76 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)169-179
Number of pages11
JournalJACC: Basic to Translational Science
Issue number2
Publication statusPublished - Feb 2020


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