Impaired sinoatrial node function and increased susceptibility to atrial fibrillation in mice lacking natriuretic peptide receptor C

作者：Emmanuel E. Egom, Kimberly Vella, Rui Hua, Hailey J. Jansen, Motahareh Moghtadaei, Iuliia Polina, Oleg Bogachev, Rhea Hurnik, Martin Mackasey, Sara A. Rafferty, Gibanananda Ray, Robert A. Rose · 发表于：The Journal of Physiology · 年份：2014 · DOI：10.1113/jphysiol.2014.283135 · 被引用次数：70 · 研究领域：Heart Failure Treatment and Management、Cardiac electrophysiology and arrhythmias

Key points Natriuretic peptides (NPs) elicit their effects via multiple NP receptors (including NPR‐A, NPR‐B and NPR‐C, with NPR‐C being relatively poorly understood). We have studied the effects of NPR‐C ablation on cardiac structure, function and arrhythmogenesis using NPR‐C knockout (NPR‐C −/− ) mice. NPR‐C −/− mice are characterized by sinoatrial node (SAN) dysfunction and a profound increase in susceptibility to atrial fibrillation. Increased susceptibility to arrhythmias in NPR‐C −/− mice was associated with slowed electrical conduction in the SAN as well as the right and left atria due to enhanced collagen expression and deposition in the atria (structural remodelling), but without changes in action potential morphology (electrical remodelling) in isolated SAN or atrial myocytes. This study demonstrates a critical protective role for NPR‐C in the heart. Abstract Natriuretic peptides (NPs) are critical regulators of the cardiovascular system that are currently viewed as possible therapeutic targets for the treatment of heart disease. Recent work demonstrates potent NP effects on cardiac electrophysiology, including in the sinoatrial node (SAN) and atria. NPs elicit their effects via three NP receptors (NPR‐A, NPR‐B and NPR‐C). Among these receptors, NPR‐C is poorly understood. Accordingly, the goal of this study was to determine the effects of NPR‐C ablation on cardiac structure and arrhythmogenesis. Cardiac structure and function were assessed in wild‐type (NPR‐C +/+ )...