To test the hypothesis that the asymmetry in the afferent traffic of the intra-right atrium (RA) ATP-triggered vagal reflex is due to the stimulation by ATP of extrapulmonary (i.e., cardiac) vagal chemosensitive afferent terminals, ATP, adenosine, and capsaicin were given into the canine RA and the aortic root (AR; n = 12); ATP and adenosine were also administered into the left common carotid artery and the descending aorta (n = 6). The negative chronotropic action [i.e., suppression of sinus node (SN) automaticity] of the test compounds and time to peak effect (tp) were determined. Under baseline conditions, ATP given into the left common carotid artery had a relatively very small effect. ATP given into the descending aorta had no effect. In contrast, intra-RA and intra-AR ATP markedly suppressed SN automaticity, the former less than the latter; the opposite was true for capsaicin. Intra-RA adenosine was much less potent than intra-RA ATP. The tp of intra-RA ATP and intra-RA adenosine were larger than the tp of intra-AR ATP. Pulmonary denervation did not alter the effects of intra-RAATP, intra-ARATP, or intra-AR capsaicin but almost abolished the effect of intra-RA capsaicin. Subsequent bilateral, but not left, cervical vagotomy markedly reduce the effects of ATP and eliminated the difference between the effects of ATP and adenosine. In addition, tp of intra-RA ATP and intra-AR ATP increased substantially and were similar to tp of adenosine. It was concluded that 1) ATP can stimulate vagal afferent terminals not only in the lungs but also in the heart, 2) the latter constitutes the vagal component of the negative chronotropic action of intra-RA or intra-AR ATP on SN automatically, and 3) the asymmetry in the vagal afferent traffic elicited by ATP in the heart (i.e., right vagal dominance) supersedes the symmetrical vagal afferent traffic triggered by intrapulmonary ATP.
Mechanisms of action of CCK to activate central vagal afferent terminals