PERTUSSIS-TOXIN-SENSITIVE EFFECTS OF DIPYRIDAMOLE ON RAT ATRIAL RATE

1 In the spontaneously beating rat isolated atria the effects of dipyridamole (0.01, 0.1, 1 and 10 muM) and of adenosine (10 muM) on the chronotropic responses to exogenous noradrenaline (NA) were compared. 2 Dipyridamole (0.01 muM) reduced the chronotropic responses to NA throughout the entire concentration-response curve. A decrease in the maximal response to the agonist was also observed. 3 Neither the spontaneous outflow of [H-3]-NA nor its metabolic distribution were altered by dipyridamole (0.01 muM). 4 As observed with dipyridamole, the concentration-response curve to NA was shifted to the right by 10 muM adenosine. 8-Phenyltheophylline (8-PT), 10 muM prevented the decrease in the chronotropic response to NA produced by both 10 muM adenosine and 0.01 muM dipyridamole. 5 The preincubation of rat atria with 1 mug ml-1 pertussis toxin prevented the diminution in the chronotropic responses to NA produced by 0.01 muM dipyridamole. 6 The present results suggest that the decrease caused by dipyridamole in rat atrial chronotropic responses involves the participation of adenosine, probably through the interaction with type A1 adenosine receptors.