PACAP-27 causes negative and positive dromotropic effects in anesthetized dogs

While pituitary adenylate cyclase-activating polypeptide (PACAP) has been identified radioimmunologically in the rat heart, the physiological role of PACAP has not been elucidated in the regulation of the atrioventricular conduction in the heart. We, therefore, determined the dromotropic effects of PACAP-27 injected into the cannulated atrioventricular node artery in the autonomically decentralized heart of the open-chest, anesthetized dog. PACAP-27 caused transient positive followed by negative dromotropic responses in a dose-dependent manner, whereas vasoactive intestinal peptide (VIP) caused only a positive dromotropic response. Atropine and tetrodotoxin blocked the negative dromotropic response to PACAP-27 and after blockade PACAP-27 caused only a positive dromotropic response. Tetrodotoxin and propranolol did not affect the positive dromotropic response to PACAP-27 in atropine-treated dogs. PACAP-27 altered the atrio-His bundle interval but did not alter the His-ventricle interval. These results demonstrate that PACAP-27 prolongs the atrio-His bundle interval due to the liberation of acetylcholine from parasympathetic nerves and decreases it by a non-adrenergic mechanism in the dog heart in situ.