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.
Herring
N
N
University Laboratory of Physiology, Oxford, United Kingdom.
Zaman
J A
JA
Paterson
D J
DJ
D000109:Acetylcholine / Q000493:pharmacokinetics; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism* / Q000494:pharmacology; D001919:Bradycardia / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006162:Guanylate Cyclase / Q000235:genetics; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D020105:Milrinone / Q000494:pharmacology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism / Q000494:pharmacology; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics; D013449:Sulfonamides; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014316:Tritium; D014630:Vagus Nerve / Q000502:physiology*; D020960:omega-Conotoxins / Q000494:pharmacology; D000099242:Atrial Natriuretic Factor Receptor B
D000109:Acetylcholine; D009320:Atrial Natriuretic Factor; D002121:Calcium Channel Blockers; D002217:Carbachol; D002316:Cardiotonic Agents; D006152:Cyclic GMP; D004791:Enzyme Inhibitors; D006162:Guanylate Cyclase; D007546:Isoquinolines; D020105:Milrinone; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009569:Nitric Oxide; D010726:Phosphodiesterase Inhibitors; D011134:Polysaccharides; D012333:RNA, Messenger; D017461:Receptors, Atrial Natriuretic Factor; D013449:Sulfonamides; D014316:Tritium; D020960:omega-Conotoxins; D000099242:Atrial Natriuretic Factor Receptor B; C072551:HS 142-1; C091715:atrial natriuretic factor receptor A; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide