Adenosine and prostacyclin independent electrophysiological effects of dipyridamole in guinea-pig papillary muscles and canine cardiac Purkinje fibers.
Dipyridamole was initially introduced as a coronary vasodilator. The exact mechanism of action of dipyridamole on the coronary vasculature is unknown, but proposed mechanisms of action include inhibition of adenosine uptake, increased myocardial prostacyclin production and inhibition of phosphodiesterase activity. The purpose of our study was to examine the electrophysiological effects of dipyridamole on guinea-pig papillary muscles and canine cardiac Purkinje fibers to determine whether similar mechanisms might account for the electrophysiological effects of this compound. Conventional microelectrode techniques were used to record transmembrane action potentials from either guinea-pig papillary muscles or canine cardiac Purkinje fibers. Dipyridamole produces a dose-dependent prolongation of action potential duration with a threshold concentration of approximately 5 X 10(-7) M in tissues from either species. Dipyridamole (10(-5) M) increases action potential amplitude (124 +/- 1 to 127 +/- 1 mV), increases action potential duration (119 +/- 6 to 146 +/- 5 msec) and produces hyperpolarization of the resting potential (-85 +/- 1 to -87 +/- 1 mV) in guinea-pig papillary muscles (n = 27, P less than .05). Dipyridamole (10(-5) M) increases action potential duration (276 +/- 5 to 293 +/- 5 msec) in canine cardiac Purkinje fibers (n = 21, P less than .05). The effects of dipyridamole (5 X 10(-7) M) are neither accentuated by adenosine (10(-4) M) nor attenuated by adenosine deaminase (1 U/ml) Pretreatment with indomethacin (10(-5) M) does not block these effects. Dipyridamole (10(-5) M) produces a negative chronotropic response in canine Purkinje fibers, increases mean escape intervals from 4.9 +/- 0.9 to 7.8 +/- 1.4 sec (n = 8, P less than .05) and fails to suppress slow response action potentials in 22 mM K+ depolarized tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000037:antagonists & inhibitors; D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D004176:Dipyridamole / Q000494:pharmacology*; D004285:Dogs; D011464:Epoprostenol / Q000502:physiology*; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology
D004176:Dipyridamole; D011464:Epoprostenol; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D000241:Adenosine; D007545:Isoproterenol; D011188:Potassium; D007213:Indomethacin