Author + information
- Received September 16, 2019
- Revision received November 19, 2019
- Accepted November 19, 2019
- Published online February 24, 2020.
- Lakshini Y. Herat, PhDa,
- Aaron L. Magno, PhDb,
- Caroline Rudnicka, BSc (Hons)b,
- Jana Hricova, BSc, MSca,
- Revathy Carnagarin, MBBS, MS, MD, PhDc,
- Natalie C. Ward, PhDd,e,f,
- Angelique Arcambal, PhDd,g,
- Marcio G. Kiuchi, MD, MSc, PhDc,
- Geoff A. Head, PhDh,
- Markus P. Schlaich, MDc,i,∗∗ ( and )
- Vance B. Matthews, PhDa,∗
- aDobney Hypertension Centre, School of Biomedical Science, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia
- bResearch Centre, Royal Perth Hospital, Perth, Australia
- cDobney Hypertension Centre, School of Medicine, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia
- dSchool of Medicine, Royal Perth Hospital, University of Western Australia, Perth, Australia
- eSchool of Public Health, Curtin University, Perth, Australia
- fCurtin Health Innovation Research Institute, Curtin University, Perth, Australia
- gUniversité de La Réunion, Saint-Denis, Réunion, France
- hBaker Heart and Diabetes Institute, Melbourne, Australia
- iDepartment of Cardiology and Department of Nephrology, Royal Perth Hospital, Perth, Australia
- ↵∗Address to correspondence:
Dr. Markus P. Schlaich, Dobney Chair in Clinical Research, School of Medicine - Royal Perth Hospital Unit, The University of Western Australia, Level 3, MRF Building, Rear 50 Murray Street, Perth WA 6000, Australia.
• SGLT2 inhibitors improve cardiovascular outcomes.
• SGLT2 inhibitor–induced sympathetic nervous system inhibition may be an underlying mechanism.
• Chemical denervation in neurogenic hypertensive mice reduces renal SGLT2 expression.
• SGLT2 inhibition lowered blood pressure and resulted in significantly reduced tyrosine hydroxylase and norepinephrine levels in the kidney tissue of neurogenic hypertensive mice.
• Crosstalk between the sympathetic nervous system and SGLT2 regulation appears as a key mechanism of the cardiorenal protective effects demonstrated with SGLT2 inhibition.
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.
↵∗ Drs. Schlaich and Matthews contributed equally to this work and are joint senior authors.
The authors kindly acknowledge funding from the Royal Perth Hospital Research Foundation and Diabetes Research Western Australia awarded to Drs. Schlaich and Matthews. Dr. Head is supported by a National Health and Medical Research Council Research Fellowship and has received research grant support from Boehringer Ingelheim. Prof. Schlaich is supported by a National Health and Medical Research Council Research Fellowship and has received research support from Medtronic, Abbott, Novartis, Servier, Pfizer, and Boehringer Ingelheim. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received September 16, 2019.
- Revision received November 19, 2019.
- Accepted November 19, 2019.
- 2020 The Authors