Effects of PACAP-38 on the SA nodal pacemaker activity in autonomically decentralized hearts of anesthetized dogs

Pituitary adenylate cyclase-activating polypeptide (PACAP) receptors exist, but the physiologic role of PACAP is unclear in the heart in situ. We investigated effects of PACAP-38 on sinus rate and on the negative chronotropic response to acetylcholine (ACh) or stimulation of the intracardiac parasympathetic nerve fibers to the sinoatrial nodal region in the autonomically decentralized heart of the open-chest, anesthetized dog. PACAP-38 (0.1-1 nmol) injected directly into the sinus node artery caused transient positive followed by negative chronotropic responses. Both pretreatment with atropine and tetrodotoxin inhibited the 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 results suggest that (a) PACAP-38 induces negative chronotropic responses and liberates ACh from intracardiac postganglionic parasympathetic nerves, and that (b) PACAP-38 reduces ACh-induced atrial fibrillation threshold in the dog heart in situ.