Basic study of mechanism that neuropeptide PACAP induces paroxysmal atrial fibrillation.

1999 Fiscal Year Final Research Report Summary

• Project/Area Number: 10670082
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Shinshu University
• Principal Investigator: NAKANE Tokio Shinshu Univ. Sch. Medicine Asc. Professor, 医学部, 助教授 (40155776)
• Co-Investigator(Kenkyū-buntansha): HIROSE Masamichi Shinshu Univ. Sch. Medicine Instructor, 医学部, 助手 (40273081)
• Project Period (FY): 1998 – 1999
• Keywords: PACAP / arrhythmia / atrial fibrillation / parasympathetic nerve / vagal stimulation / sinus node / β-adrenoceptors / muscarinic receptors

Research Abstract

We reported that pituitary adenylate cyclase activating polypeptide-27 (PACAP-27) induces atrial fibrillation (AF)spontaneously. To investigate how PACAP indues AF, we examined the effects of PACAP and vagal stimulation (VS) on the electrophysiological variables in anesthetized canine atrium. At first, we obtained the epicardial activation sequence of the right atrium from 42 unipolar recording electrodes. PACAP-27 prolonged and shortened conduction time, although VS slightly prolonged it. Second, using 95 bipolar electrodes fixed to right and left atria, we compared the effects of PACAP-27 and VS on the electrophysiological variables at high or low site of both atria. PACAP-27 induced AF more frequently than VS. PACAP-27 shortened the effective refractory period (ERP) and the wavelength at all of the 4 atrial sites, but VS shortened them at only the high fight atrium. Global dispersion of ERP were less after PACAP-27 than VS. Therefore, increased global dispersion of refractoriness is not required for the initiation of AF. Global shortening and the conduction properties of premature beats contribute to the greater profibrillatory effect of PACAP-27. After atropine treatment, none of the interventions changed ERP, suggesting that PACAP-27 activates intrinsic cardiac nerves that are distributed throughout both atria, not all of which are activated by cervical VS.
To test the hypothesis that the pacemaker activities correlate with the densities of β-adrenoceptors and muscarinic receptors, we performed radioligand receptor assay using [ィイD1125ィエD1I]CYP and [ィイD13ィエD1H]QNB compared the receptor densities in 4 regions (upper, sinoatrial node area, bottom and appendage) of right atrium. The dissociation constants and densities of β-adrenoceptors were not differed in the 4 regions. Although the densities of muscarinic receptors in sinoatrial node region were significantly higher than those in the other regions, the constants were almost the same in the 4 regions.