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 en hancing 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 natriur etic peptide (CNP) were evaluated in isolated guinea pig atrial-right vagal nerve preparations. RT-PCR confirmed the presence NPR B and A receptor mRN A 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 n o effect on the HR response to carbamylcholine and facilitated the release of [H-3] acetylcholine during atrial field stimulation. The particulate gua nylyl cyclase-coupled receptor antagonist HS-142-1, the phosphodiesterase 3 inhibitor milrinone, the protein kinase A inhibitor H89, and the N-type ca lcium channel blocker <omega>-conotoxin all blocked the effect of CNP on va gal-induced bradycardia. Like NO, BNP and CNP facilitate vagal neurotransmi ssion and bradycardia. This may occur via a cGMP-PDE3-dependent pathway inc reasing cAMP-PKA-dependent phosphorylation of presynaptic N-type calcium ch annels.