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

D. P. Rardon, R. J. Kovacs, J. C. Bailey

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 languageEnglish (US)
Pages (from-to)206-213
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume231
Issue number1
StatePublished - Jan 1 1984

Fingerprint

Purkinje Fibers
Dipyridamole
Papillary Muscles
Epoprostenol
Adenosine
Canidae
Guinea Pigs
Action Potentials
Phosphoric Diester Hydrolases
Membrane Potentials
Adenosine Deaminase
Microelectrodes
Vasodilator Agents
Indomethacin

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

@article{2ac709b7ddd34ea59a48fac58fb0d256,
title = "Adenosine and prostacyclin independent electrophysiological effects of dipyridamole in guinea-pig papillary muscles and canine cardiac Purkinje fibers",
abstract = "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.",
author = "Rardon, {D. P.} and Kovacs, {R. J.} and Bailey, {J. C.}",
year = "1984",
month = "1",
day = "1",
language = "English (US)",
volume = "231",
pages = "206--213",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "1",

}

TY - JOUR

T1 - Adenosine and prostacyclin independent electrophysiological effects of dipyridamole in guinea-pig papillary muscles and canine cardiac Purkinje fibers

AU - Rardon, D. P.

AU - Kovacs, R. J.

AU - Bailey, J. C.

PY - 1984/1/1

Y1 - 1984/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0021225582&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021225582&partnerID=8YFLogxK

M3 - Article

C2 - 6092602

AN - SCOPUS:0021225582

VL - 231

SP - 206

EP - 213

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 1

ER -