Regional differences in cardiac effects of pituitary adenylate cyclase-activating polypeptide-27 in the isolated dog heart.
Recent observations indicate that several neuropeptides may be involved in the regulation of cardiac function, but the effects of these peptides on the atrium are not always the same as those on the ventricle. To compare the effect of pituitary adenylate cyclase-activating polypeptide (PACAP)-27 on the atrium with that on the ventricle, we investigated the effects of PACAP-27 on the sinus rate and atrial and ventricular contractility in isolated, blood-perfused dog heart preparations. PACAP-27 (0.01-0.3 nmol) caused transient positive followed by negative chronotropic and inotropic responses in a dose-dependent manner in the isolated right atrium, whereas it caused only a dose-dependent positive inotropic response in the left ventricle. After atropine treatment, PACAP-27 caused only positive cardiac responses in isolated atria. The order of the increase in response to PACAP-27 was atrial contractile force > sinus rate > or = ventricular contractile force. Tetrodotoxin blocked the negative chronotropic and inotropic responses to PACAP-27 in isolated atria. Propranolol did not affect the positive response. PACAP-(6-27), a type I PACAP receptor antagonist, attenuated the positive responses similarly in the atropine-treated right atrium and the left ventricle. Thus, we demonstrated that (1) PACAP-27 caused negative cardiac effects in the atrium and sinoatrial node by activation of intracardiac parasympathetic nerves, but had no negative effect on the ventricle; (2) PACAP-27 had positive effects in the atrium, sinoatrial node and ventricle mediated by type I PACAP receptors, but PACAP-27 was more effective in the atrium and sinoatrial node than in the ventricle of the dog heart.
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
M
M
Hirose
Y
Y
Furukawa
M
M
Lakhe
S
S
Chiba
D000818:Animals; D016275:Atrial Function; D004285:Dogs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D013779:Tetrodotoxin / Q000494:pharmacology; D016276:Ventricular Function
D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C106317:pituitary adenylate-cyclase-activating peptide (6-27); D013779:Tetrodotoxin