Natriuretic peptides modulate heart rate, electrical conduction and arrhythmogensis in vivo

Abstract

Natriuretic peptides (NPs) are a family of cardioprotective hormones including B-type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). NPs elicit their effects via three receptors denoted NPR-A (binds BNP), NPR-B (binds CNP) and NPR-C (binds all NPs). In this study we performed electrocardiograms (ECG) and programmed stimulation protocols to study the effects of BNP, CNP and their NPRs on heart rate (HR), electrical conduction, and susceptibility to atrial fibrillation (AF). Acute injection of BNP and CNP increased HR in wildtype animals, whereas selective activation of NPR-C decreased HR. No differences in HR, sinus node function or blood pressure were observed in NPR-C-/- mice compared to wildtype (NPR-C+/+) and heterozygote (NPR-C+/-) littermates. However, NPR-C-/- mice are more susceptible to AF compared to wildtype controls. These experiments provide novel insight into the direct electrophysiological effects of NPs and their receptors in the heart.