Effects of repetitive vagal stimulation on heart rate and on cardiac vasoactive intestinal polypeptide efflux

• Published in: The American journal of physiology Vol. 268; no. 5 Pt 2; p. H1939
• Main Authors: Hill, M R, Wallick, D W, Martin, P J, Levy, M N
• Format: Journal Article
• Language: English
• Published: United States 01.05.1995
• Subjects: Animals; Dogs; Electric Stimulation; Heart Atria - drug effects; Heart Rate; In Vitro Techniques; Myocardium - metabolism; Sinoatrial Node - physiology; Tachycardia - etiology; Tachycardia - physiopathology; Time Factors; Vagus Nerve - physiology; Vasoactive Intestinal Peptide - metabolism; Vasoactive Intestinal Peptide - pharmacology
• ISSN: 0002-9513
• DOI: 10.1152/ajpheart.1995.268.5.h1939

In dogs anesthetized with alpha-chloralose, we assessed the "vagally induced tachycardia" elicited by successive 2-min periods of intense vagal stimulation (0.5 ms, 10 mA, 20 Hz) after we had blocked the animals' muscarinic and beta-adrenergic receptors with atropine and propranolol, respectively. We found that the tachycardia produced by the successive vagal stimulations progressively decreased to < 20% of the initial tachycardia response within 84 min. We also observed that the chronotropic response to vasoactive intestinal polypeptide (VIP) injected into the sinus node artery after the vagal stimulation regimen did not differ significantly from the response to the same dose of VIP injected prior to vagal stimulation. This finding indicates that the postjunctional responsiveness of the cardiac pacemaker cells had not diminished over the course of the vagal stimulation regimen. In isolated, perfused right atrial preparations, we observed a close correlation between the efflux of VIP from the atrial tissues and the chronotropic responses to vagal stimulation. Our results support the hypotheses that 1) VIP is a mediator of vagally induced tachycardia, 2) the reduction in VIP efflux is associated with a diminished vagally induced tachycardia, and 3) the reduced efflux of VIP probably reflects a diminution in neuronal release, perhaps by depletion of this peptide from the vagus nerve endings consequent to the prolonged neural stimulation.