EFFECTS OF PACAP-38 ON THE SA NODAL PACEMAKER ACTIVITY IN AUTONOMICALLY DECENTRALIZED HEARTS OF ANESTHETIZED DOGS

Pituitary adenylate cyclase-activating polypeptide (PACAP) receptors e xist, but the physiologic role of PACAP is unclear in the heart in sit u. We investigated effects of PACAP-38 on sinus rate and on the negati ve chronotropic response to acetylcholine (ACh) or stimulation of the intracardiac parasympathetic nerve fibers to the sinoatrial nodal regi on in the autonomically decentralized heart of the open-chest, anesthe tized dog. PACAP-38 (0.1-1 nmol) injected directly into the sinus node artery caused transient positive followed by negative chronotropic re sponses. Both pretreatment with atropine and tetrodotoxin inhibited th e negative chronotropic responses to PACAP-38. However, hexamethonium did not block the negative responses to PACAP-38. After treatment with PACAP-38 (0.1-1 nmol), ACh induced atrial fibrillation significantly (p < 0.01). On the other hand, the negative chronotropic responses to intracardiac parasympathetic stimulation were not changed. These resul ts suggest that (a) PACAP-38 induces negative chronotropic responses a nd liberates ACh from intracardiac postganglionic parasympathetic nerv es, and that (b) PACAP-38 reduces ACh-induced atrial fibrillation thre shold in the dog heart in situ.