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-Phe6,Leu17]VIP, and NT-VIP, to evaluate the role of VIP as a mediator of vagally induced tachycardia in chloralose-anesthetized dogs. After we administered muscarinic and beta-adrenergic receptor antagonists, we evoked vagally induced tachycardia either directly, by stimulating the vagus nerves for 2 min, or reflexly, by injecting phenylephrine to increase blood pressure. Furthermore, each of the antagonists attenuated the tachycardias induced by vagal stimulation by approximately 50% and the reflexly induced tachycardias by approximately 70%. Each VIP antagonist attenuated the chronotropic responses that we evoked by injecting VIP (5.2 ng/kg) into the sinus node artery. We tested the specificity of these VIP antagonists by determining whether they attenuated the increases in heart rate evoked by two other neuropeptides [peptide histidine isoleucine (PHI) and glucagon]. VIP-(10-28) attenuated the response to PHI, but not to glucagon. The other two VIP antagonists 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.
D000818:Animals; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009496:Neurotensin; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011993:Recombinant Fusion Proteins; D013610:Tachycardia / Q000209:etiology* / Q000503:physiopathology*; D014630:Vagus Nerve / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D010446:Peptide Fragments; D010455:Peptides; D011993:Recombinant Fusion Proteins; C048507:vasoactive intestinal peptide, 4-chloro-Phe(6)-Leu(17)-; C069189:(VIP-neurotensin) hybrid antagonist; D014660:Vasoactive Intestinal Peptide; D009496:Neurotensin; C047945:vasoactive intestinal peptide (10-28)