title: Vasoactive intestinal polypeptide receptor antagonism enhances the vagally induced increase in cardiac interval of the rat atrium in vitro.
abstract: The effect of vasoactive intestinal polypeptide (VIP) receptor antagonism on preganglionic vagal electrical stimulation and on vagal postganglionic activation using nicotine and 1,1-dimethyl-4-phenylpiperazinium iodide on cardiac interval was evaluated in the isolated innervated rat right atrium. The vagus was stimulated at 4, 8, 16 and 32 Hz, pulse duration 1 ms, 20 V, for 30 s. All experiments were carried out in the presence of atenolol (4 microM). Vagal stimulation caused a frequency-dependent increase in cardiac interval which was amplified significantly at each frequency, except at 32 Hz, following application of the VIP receptor antagonist VIP(6-28) at 2 nM in 15 rats. Application of the ganglionic antagonist hexmethonium (28 microM, n = 7 rats) prior to 2 nM VIP(6-28) abolished this effect. Increasing the concentration of VIP(6-28) 10-fold to 20 nM did not result in a greater increase in cardiac interval than that obtained at 2 nM. Nicotine (0.1, 0.3, 0.5, 1.0 and 2.0 mM) increased cardiac interval by direct activation of postganglionic vagal fibres, but 2 nM VIP(6-28) did not affect the nicotine concentration response (n = 6 rats). 1,1-Dimethyl-4-phenylpiperazinium iodide (25, 50, 100 and 200 microM; n = 6 rats) was also used to induce an increase in cardiac interval; again it was not significantly altered by 2 nM VIP(6-28). Therefore, VIP receptor antagonism enhances the magnitude of vagally induced cardiac slowing, probably via an action at the preganglionic-postganglionic synapse.
authors.affiliation: School of Pharmacy & Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: K
authors.initials: K
authors.lastname: Hogan
authors.forename: F
authors.initials: F
authors.lastname: Markos
mesh_terms: D000818:Animals; D016275:Atrial Function / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009538:Nicotine / Q000008:administration & dosage; D010446:Peptide Fragments / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage*
chemical_list: D010446:Peptide Fragments; D018005:Receptors, Vasoactive Intestinal Peptide; C113198:vasoactive intestinal peptide (6-28); D014660:Vasoactive Intestinal Peptide; D009538:Nicotine