VASOACTIVE INTESTINAL POLYPEPTIDE ANTAGONISTS ATTENUATE VAGALLY INDUCED TACHYCARDIA IN THE ANESTHETIZED DOG

We used three vasoactive intestinal polypeptide (VIP) antagonists, VIP -(10-28), [p-Cl-D-Phe(6),Leu(17)]VIP, and NT-VIP, to evaluate the role of VIP as a mediator of vagally induced tachycardia in chloralose-ane sthetized dogs. After we administered muscarinic and P-adrenergic rece ptor antagonists, we evoked vagally induced tachycardia either directl y, by stimulating the vagus nerves for 2 min, or reflexly, by injectin g phenylephrine to increase blood pressure. Furthermore, each of the a ntagonists attenuated the tachycardias induced by vagal stimulation by similar to 50% and the reflexly induced tachycardias by similar to 70 %. Each VIP antagonist attenuated the chronotropic responses that we e voked by injecting VIP (5.2 ng/kg) into the sinus node artery. We test ed the specificity of these VIP antagonists by determining whether the y attenuated the increases in heart rate evoked by two other neuropept ides [peptide histidine isoleucine (PHI) and glucagon]. VIP-(10-28) at tenuated the response to PHI, but not to glucagon. The other two VIP a ntagonists did not alter the chronotropic responses to PHI or glucagon . Our results support the hypothesis that neurally released VIP is the principal mediator of vagally induced tachycardia in the dog.