JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rardon, D. P.
Right arrow Articles by Bailey, J. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rardon, D. P.
Right arrow Articles by Bailey, J. C.

Adenosine and prostacyclin independent electrophysiological effects of dipyridamole in guinea-pig papillary muscles and canine cardiac Purkinje fibers

DP Rardon, RJ Kovacs and JC Bailey

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)

Volume 231, Issue 1, pp. 206-213, 10/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics






Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1984 by the American Society for Pharmacology and Experimental Therapeutics.