Natriuretic Peptide Receptor-C Protects Against Angiotensin II-Mediated Sinoatrial Node Disease in Mice

Martin Mackasey, BSc; Emmanuel E. Egom, MD, PhD; Hailey J. Jansen, PhD; Rui Hua, PhD; Motahareh Moghtadaei, PhD; Yingjie Liu, PhD; Jaspreet Kaur, PhD; Megan D. McRae, BHSc; Oleg Bogachev, MD; Sara A. Rafferty, MSc; Gibanananda Ray, PhD; Adam W. Kirkby, MSc; Robert A. Rose, PhD

JACC: Basic to Translational Science (Dec 2018)

Natriuretic Peptide Receptor-C Protects Against Angiotensin II-Mediated Sinoatrial Node Disease in Mice

Martin Mackasey, BSc,
Emmanuel E. Egom, MD, PhD,
Hailey J. Jansen, PhD,
Rui Hua, PhD,
Motahareh Moghtadaei, PhD,
Yingjie Liu, PhD,
Jaspreet Kaur, PhD,
Megan D. McRae, BHSc,
Oleg Bogachev, MD,
Sara A. Rafferty, MSc,
Gibanananda Ray, PhD,
Adam W. Kirkby, MSc,
Robert A. Rose, PhD

Affiliations

Martin Mackasey, BSc: Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada, and Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
Emmanuel E. Egom, MD, PhD: Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
Hailey J. Jansen, PhD: Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada, and Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
Rui Hua, PhD: Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
Motahareh Moghtadaei, PhD: Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
Yingjie Liu, PhD: Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada, and Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Jaspreet Kaur, PhD: Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada, and Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Megan D. McRae, BHSc: Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada, and Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Oleg Bogachev, MD: Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
Sara A. Rafferty, MSc: Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
Gibanananda Ray, PhD: Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
Adam W. Kirkby, MSc: Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada, and Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Robert A. Rose, PhD: Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada, and Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Address for correspondence: Prof. Robert Alan Rose, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, GAC66, Health Research Innovation Centre, 3280 Hospital Drive NW, Calgary, Alberta T2N 4Z6, Canada.

Journal volume & issue: Vol. 3, no. 6
pp. 824 – 843

Abstract

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Summary: Sinoatrial node (SAN) disease mechanisms are poorly understood, and therapeutic options are limited. Natriuretic peptide(s) (NP) are cardioprotective hormones whose effects can be mediated partly by the NP receptor C (NPR-C). We investigated the role of NPR-C in angiotensin II (Ang II)-mediated SAN disease in mice. Ang II caused SAN disease due to impaired electrical activity in SAN myocytes and increased SAN fibrosis. Strikingly, Ang II treatment in NPR-C−/− mice worsened SAN disease, whereas co-treatment of wild-type mice with Ang II and a selective NPR-C agonist (cANF) prevented SAN dysfunction. NPR-C may represent a new target to protect against the development of Ang II-induced SAN disease. Key Words: fibrosis, hypertension, ion currents, natriuretic peptide, sinoatrial node

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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