Vasoactive intestinal polypeptide antagonists attenuate vagally
induced tachycardia in the anesthetized dog.
Hill, Michael R. S., Don W. Wallick, Luc R. Mongeon, Paul J. Martin,
and Matthew N. Levy.
Division of Investigative Medicine The Mt. Sinai Medical Center,
and Department of Biomedical Engineering, Case Western Reserve
University, Cleveland, Ohio
APStracts 2:0227H, 1995.
We used three VIP antagonists, 1) VIP(10-28), 2) [p-Cl-D-Phe6,Leu17]
-VIP, and 3) 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 about
50%, and the reflexly induced tachycardias by about 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.
Received 3 February 1995; accepted in final form 26 May 1995.
APS Manuscript Number H98-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 June 1995.