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 < .05). Dipyridamole (10-5 M) increases action potential duration (276 ± 5 to 293 ± 5 msec) in canine cardiac Purkinje fibers (n = 21, P < .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 < .05) and fails to suppress slow response action potentials in 22 mM K+ depolarized tissues. Dipyridamole produces action potential prolongation in cardiac ventricular tissues, a negative chronotropic effect in canine cardiac Purkinje fibers and depresses developed tension in guinea-pig papillary muscles (8.0 ± 0.6 to 6.5 ± 0.6 g/mm2, n = 7, P < .05), effects opposite to those expected of a compound producing significant phosphodiesterase inhibition. We conclude: 1) dipyridamole produces electrophysiologic effects in guinea-pig papillary muscles and canine cardiac Purkinje fibers; and 2) these effects appear to be independent of adenosine uptake inhibition, prostacyclin production or phosphodiesterase inhibition.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1984|
ASJC Scopus subject areas
- Molecular Medicine