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Experimental Physiology 91.3 pp 641-646
DOI: 10.1113/expphysiol.2006.033605
© The Physiological Society 2006
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Vasoactive intestinal polypeptide receptor antagonism enhances the vagally induced increase in cardiac interval of the rat atrium in vitro

K. Hogan1 and F. Markos1

1 School of Pharmacy & Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland

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 µM). 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 µM, 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 µM; 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.

(Received 14 February 2006; accepted after revision 6 March 2006; first published online 9 March 2006)
Corresponding author F. Markos: School of Pharmacy & Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland. Email: hazmarkos{at}yahoo.com







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