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 microM) and of adenosine (10 microM) on the chronotropic responses to exogenous noradrenaline (NA) were compared. 2. Dipyridamole (0.01 microM) 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 [3H]-NA nor its metabolic distribution were altered by dipyridamole (0.01 microM). 4. As observed with dipyridamole, the concentration-response curve to NA was shifted to the right by 10 microM adenosine. 8-Phenyltheophylline (8-PT), 10 microM prevented the decrease in the chronotropic response to NA produced by both 10 microM adenosine and 0.01 microM dipyridamole. 5. The preincubation of rat atria with 1 micrograms ml-1 pertussis toxin prevented the diminution in the chronotropic responses to NA produced by 0.01 microM 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.