SGLT2 Inhibitor–Induced Sympathoinhibition

Lakshini Y. Herat, PhD; Aaron L. Magno, PhD; Caroline Rudnicka, BSc (Hons); Jana Hricova, BSc, MSc; Revathy Carnagarin, MBBS, MS, MD, PhD; Natalie C. Ward, PhD; Angelique Arcambal, PhD; Marcio G. Kiuchi, MD, MSc, PhD; Geoff A. Head, PhD; Markus P. Schlaich, MD; Vance B. Matthews, PhD

JACC: Basic to Translational Science (Feb 2020)

SGLT2 Inhibitor–Induced Sympathoinhibition

Lakshini Y. Herat, PhD,
Aaron L. Magno, PhD,
Caroline Rudnicka, BSc (Hons),
Jana Hricova, BSc, MSc,
Revathy Carnagarin, MBBS, MS, MD, PhD,
Natalie C. Ward, PhD,
Angelique Arcambal, PhD,
Marcio G. Kiuchi, MD, MSc, PhD,
Geoff A. Head, PhD,
Markus P. Schlaich, MD,
Vance B. Matthews, PhD

Affiliations

Lakshini Y. Herat, PhD: Dobney Hypertension Centre, School of Biomedical Science, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia
Aaron L. Magno, PhD: Research Centre, Royal Perth Hospital, Perth, Australia
Caroline Rudnicka, BSc (Hons): Research Centre, Royal Perth Hospital, Perth, Australia
Jana Hricova, BSc, MSc: Dobney Hypertension Centre, School of Biomedical Science, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia
Revathy Carnagarin, MBBS, MS, MD, PhD: Dobney Hypertension Centre, School of Medicine, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia
Natalie C. Ward, PhD: School of Medicine, Royal Perth Hospital, University of Western Australia, Perth, Australia; School of Public Health, Curtin University, Perth, Australia; Curtin Health Innovation Research Institute, Curtin University, Perth, Australia
Angelique Arcambal, PhD: School of Medicine, Royal Perth Hospital, University of Western Australia, Perth, Australia; Université de La Réunion, Saint-Denis, Réunion, France
Marcio G. Kiuchi, MD, MSc, PhD: Dobney Hypertension Centre, School of Medicine, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia
Geoff A. Head, PhD: Baker Heart and Diabetes Institute, Melbourne, Australia
Markus P. Schlaich, MD: Dobney Hypertension Centre, School of Medicine, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia; Department 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.
Vance B. Matthews, PhD: Dobney Hypertension Centre, School of Biomedical Science, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia

Journal volume & issue: Vol. 5, no. 2
pp. 169 – 179

Abstract

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Summary: 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. Key Words: denervation, heart, hypertension, kidney, SGLT2, sympathetic nervous system

Published in JACC: Basic to Translational Science

ISSN: 2452-302X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://www.journals.elsevier.com/jacc-basic-to-translational-science/

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