Differences in chronotropic and inotropic responses of canine atrial muscle and SA node pacemaker activity to adenosine and ACh.

The right atrium isolated from the dog heart was perfused through the cannulated sinus node artery with heparinized arterial blood led from a support dog anesthesized with 30 mg/Kg of sodium pentobarbital. When adenosine was administered into the sinus node artery, negative chronotropic and inotropic effects were dose-relatedly induced. The threshold dose for inducing the negative ones was 0.3 mug. Even a large dose level of 100 mug of adenosine did not cause sinus arrest although a profound sinus deceleration was induced. Adenosine action was suppressed by treatment with caffeine both in chronotropism and in inotropism. On the other hand, ACh induced only negative inotropic effect at a dose range of 0.01-0.03 mug. At 0.1 mug, ACh produced a significantly negative chronotropic effect. A large amount of 3-10 mug of ACh usually caused sinus arrest. Atropine treatment inhibited a negative chronotropic effect much more readily than a negative inotropic one. Although ACh action was enhanced by physostigmine, the difference of threshold doses remained unchanged even after physostigmine treatment. From these results, either adenosine or ACh depresses both SA nodal pacemaker activity and atrial contractile force and there may be the difference of receptor density for ACh between the SA node and atrial tissue.