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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.

Type

Journal article

Journal

Am J Physiol Heart Circ Physiol

Publication Date

12/2001

Volume

281

Pages

H2318 - H2327

Keywords

Acetylcholine, Animals, Atrial Natriuretic Factor, Bradycardia, Calcium Channel Blockers, Carbachol, Cardiotonic Agents, Cyclic GMP, Enzyme Inhibitors, Female, Gene Expression, Guanylate Cyclase, Guinea Pigs, Heart Rate, Isoquinolines, Milrinone, Natriuretic Peptide, Brain, Natriuretic Peptide, C-Type, Nitric Oxide, Phosphodiesterase Inhibitors, Polysaccharides, RNA, Messenger, Receptors, Atrial Natriuretic Factor, Sulfonamides, Synaptic Transmission, Tritium, Vagus Nerve, omega-Conotoxins