Natriuretic peptides like NO facilitate cardiac vagal neurotransmission and bradycardia via a cGMP pathway.

We tested the hypothesis that natriuretic peptide receptors (NPRs) that are coupled to cGMP production act in a similar way to nitric oxide (NO) by enhancing acetylcholine release and vagal-induced bradycardia. The effects of enzyme inhibitors and channel blockers on the action of atrial natriuretic peptide (ANP), brain-derived natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) were evaluated in isolated guinea pig atrial-right vagal nerve preparations. RT-PCR confirmed the presence NPR B and A receptor mRNA in guinea pig sinoatrial node tissue. BNP and CNP significantly (P < 0.05) enhanced the heart rate (HR) response to vagal nerve stimulation. CNP had no effect on the HR response to carbamylcholine and facilitated the release of [(3)H]acetylcholine during atrial field stimulation. The particulate guanylyl cyclase-coupled receptor antagonist HS-142-1, the phosphodiesterase 3 inhibitor milrinone, the protein kinase A inhibitor H89, and the N-type calcium channel blocker omega-conotoxin all blocked the effect of CNP on vagal-induced bradycardia. Like NO, BNP and CNP facilitate vagal neurotransmission and bradycardia. This may occur via a cGMP-PDE3-dependent pathway increasing cAMP-PKA-dependent phosphorylation of presynaptic N-type calcium channels.