Electrophysiological-anatomic correlates of atp triggered vagal reflex in the dog iv: stimulation of left ventricular vagal afferents. Katchanov, Guennadi, Jiang Xu, Anthony Clay, and Amir Pelleg. Likoff Cardiovascular Institute, Allegheny University of Health Sciences, Department of Medicine, Philadelphia, PA
APStracts 3:0496H, 1996.
We have recently shown that the mediation by the vagus nerve of the negative chronotropic action of adenosine 5-triphosphate (ATP) on the canine sinus node automaticity is the result of stimulation by ATP of extrapulmonary vagal afferent nerve terminals. To test the hypothesis that ATP stimulates vagal afferent nerve terminals in the left ventricular myocardium and thereby inducing vagus nerve mediated cardiac response, ATP and its related analogs: 2methyl-thio-ATP (2mSATP), [alpha],[beta]methylene-ATP ([alpha],[beta]mATP) and [beta],_methylene-ATP ([beta],_mATP) as well as adenosine 5 -diphosphate (ADP), adenosine 5-monophosphate (AMP) and adenosine were given, in anesthetized dogs, as bolus injections into the left main (LM) coronary artery, proximal and distal circumflex coronary arteries (Cfx) and proximal and distal left anterior descending coronary arteries (LAD); ATP was administered also into the right atrium. The effect of these purine compounds on sinus node automaticity was quantitated as the maximal prolongation of sinus cycle length. In addition, the time-to-peak-effect was also determined. Intra-right atrium ATP markedly slowed sinus node automaticity; this effect was almost abolished by bilateral cervical vagotomy. ATP induced a much greater response when administered into the LM coronary artery than into the right atrium. Time-to-peak -effect of ATP given at the former site was much shorter than the time-to-peak-effect of ATP given at the latter site. Intra-coronary adenosine either had no effect or a relatively very small effect and its time-to-peak-effect was significantly longer than that of intra -coronary ATP. Bilateral cervical vagotomy either abolished or markedly attenuated the effect of intra-coronary ATP, such that there was no difference between the actions of ATP and adenosine and their time-to-peak-effect became similar. The structure-function cascade of intra-coronary ATP and its analogs was: [alpha],[beta]mATP>2mSATP>ATP>/=[beta],_mATP> ADP>> AMP=0. The P2X-purinoceptor H0709-6R2 antagonist, pyridoxalp hosphate-6-azophenyl-2,4-disulphonic acid (PPADS), markedly attenuated the negative chronotropic action of all purine nucleotides other than 2mSATP. The effect of the latter was attenuated by PPADS but the difference between the effects of 2mSATP under baseline condition and in the presence of PPADS did not reach statistical significance. It was concluded that (i) ATP triggers a cardio-cardiac vagal depressor reflex by stimulating vagal afferent nerve terminals in the left ventricular myocardium and (ii) this action is mediated by P2x-purinoceptors. 

Received 6 August 1996; accepted in final form 29 October 1996.
APS Manuscript Number H709-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996