EFFECTS OF REPETITIVE VAGAL-STIMULATION ON HEART-RATE AND ON CARDIAC VASOACTIVE INTESTINAL POLYPEPTIDE EFFLUX

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 anim als' muscarinic and beta-adrenergic receptors with atropine and propra nolol, respectively. We found that the tachycardia produced by the suc cessive vagal stimulations progressively decreased to < 20% of the ini tial tachycardia response within 84 min. We also observed that the chr onotropic response to vasoactive intestinal polypeptide (VIP) injected into the sinus node artery after the vagal stimulation regimen did no t differ significantly from the response to the same dose of VIP injec ted prior to vagal stimulation. This finding indicates that the postju nctional responsiveness of the cardiac pacemaker cells had not diminis hed over the course of the vagal stimulation regimen. In isolated, per fused right atrial preparations, we observed a close correlation betwe en the efflux of VIP from the atrial tissues and the chronotropic resp onses 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 tachycardi a, 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.