Frequency dependence of vasoactive intestinal polypeptide release and vagally induced tachycardia in the canine heart

We evaluated the frequency dependence of vasoactive intestinal polypeptide (VIP) release from the parasympathetic nerves to the canine heart. In intact animals in the presence of beta-adrenergic receptor blockade (propranolol, 0.5 mg/kg), the cervical vagosympathetic trunks were stimulated at various frequencies before and after the administration of atropine (0.1 mg/kg). The stimulations before atropine produced a classical bradycardia that progressed to cardiac arrest when the stimulation frequency was raised above 10 to 15 Hz. After atropine, vagal stimulation at various frequencies increased heart rate. The heart rate reached a maximum increase of 21 +/- 3 beats per min at a stimulation frequency of 20 Hz. In an isolated atrial preparation in which the VIP outflow was measured, the tachycardia elicited after atropine had a frequency dependence similar to that obtained in vivo. The peak increase of 23 +/- 3% above the basal rate (95 +/- 8 beats per min) occurred at a stimulation frequency of 20 Hz. The VIP outflow paralleled the tachycardia response (r = 0.95); the maximum outflow of VIP was 172 +/- 54 pg/(min . 100 g wet wt) and was evoked at a stimulation frequency of 20 Hz. This suggests that the vagally induced tachycardia is mediated, at least partly, by VIP.