Evidence against prostaglandin mediation of the differential electrophysiologic effects of ATP versus adenosine in the canine heart.

Adenosine triphosphate (ATP) and adenosine exert negative chronotropic and dromotropic effects on the sino-atrial and atrioventricular nodes of the canine heart. The electrophysiologic action of ATP is more pronounced due, at least in part, to vagal reflexes triggered by ATP. In addition, ATP, but not adenosine, triggers the synthesis and release of prostaglandins. To determine whether this latter action of ATP is involved in the quantitative differences between the electrophysiologic effects of ATP and adenosine, the influence of the prostaglandin synthesis inhibitor, indomethacin, was studied on the actions of ATP and adenosine in 18 dogs. Indomethacin (5 mg/kg, i.v.) alone caused slight increase in sinus cycle length (from 384 +/- 16 ms to 402 +/- 16 ms; p less than 0.025) but did not affect atrioventricular conduction. In the presence of indomethacin, the negative chronotropic effects of both ATP and adenosine (3 mumol/kg each) were significantly augmented to a similar extent, proportionally: the maximal percent increase in sinus rhythm cycle length following ATP increased from 203 +/- 33 to 266 +/- 62 ms (p less than 0.025), and following adenosine increased from 44 +/- 8 to 64 +/- 20 ms (p less than 0.001). These results indicate that prostaglandins can indirectly modulate the electrophysiologic action of ATP and adenosine; however, ATP-triggered synthesis and release of prostaglandins do not play a major role in the differential electrophysiologic actions of ATP versus adenosine.