Atrial natriuretic peptide has dose-dependent, autonomically mediated effects on atrial refractoriness and repolarization in anesthetized dogs.
BACKGROUND
Atrial natriuretic peptide (ANP) may alter electrophysiological properties of the heart and possibly have a role in arrhythmogenesis. However, previous studies have yielded conflicting results and have not fully considered whether ANP's cardiac electrophysiological effects are mediated via direct actions and/or indirectly via the autonomic nervous system. This study's aim was to establish whether ANP infused at pathophysiological and pharmacological doses has significant in vivo cardiac electrophysiological effects and to determine whether these effects are directly or autonomically mediated.


RESULTS
Electrophysiologic and hemodynamic effects of ANP infusion (human ANP at 15-600 ng/kg per minute) were examined in chloralose-anesthetized dogs under conditions of varying autonomic blockade. In autonomically intact dogs (n = 12), low-dose ANP (15 ng/kg per minute) shortened atrial effective refractory period (ERP) (P < 0.001) and monophasic action potential duration (MAPD90) (P < 0.05) at 600, 500, and 400 msec atrial paced cycle lengths and reduced right atrial pressure (P < 0.05) but did not alter mean arterial pressure. After either combined vagal and beta-adrenergic blockade (vagotomy plus atropine plus propranolol, n = 7) or selective vagal blockade (n = 9), low-dose ANP no longer altered atrial ERP or MAPD90. Higher ANP doses (150 and 600 ng/kg per minute) decreased mean arterial and right atrial pressures (P < 0.001) but did not alter atrial ERP, MAPD90, or other electrophysiological parameters including atrial fibrillation threshold, ventricular ERP, and MAPD90.


CONCLUSIONS
ANP has dose-dependent, autonomically mediated effects on atrial refractoriness and repolarization.
Stambler
Bruce S
BS
Department of Medicine, McGuire Veterans Affairs Medical Center, Medical College of Virginia, Richmond, Virginia, USA. bss4@cwru.edu
Guo
Gary B
GB
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D016275:Atrial Function / Q000187:drug effects*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology* / Q000502:physiology; D004285:Dogs; D022062:Electrophysiologic Techniques, Cardiac; D006325:Heart Atria / Q000187:drug effects*; D006439:Hemodynamics; D023421:Models, Animal
D009320:Atrial Natriuretic Factor