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

摘要

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.