EFFECT OF PINACIDIL ON THE ELECTROPHYSIOLOGICAL PROPERTIES IN GUINEA-PIG PAPILLARY-MUSCLE AND RABBIT SINOATRIAL NODE

Abstract— The electrophysiological effect of the antihypertensive drug pinacidil has been examined in preparations of guinea‐pig papillary muscle and rabbit sino‐atrial node using a standard microelectrode method. In papillary muscle preparations, pinacidil (> 30 μM) shortened the action potential duration (APD), whereas it did not affect the maximum rate of rise (Vmax). Pinacidil (> 1 μM) also decreased APD of slow action potentials evoked by high K+ (27 mM) solution containing 0.2 mM Ba2+. At 30 μM, the drug reduced the Vmax of slow action potentials. In the spontaneously beating sino‐atrial node, pinacidil (> 30 μM) shortened APD. At 100 μM, it also decreased the heart rate, Vmax, action potential amplitude and the rate of diastolic depolarization. It is concluded that pinacidil modifies the electrical activity of myocardial cells probably due to an increase in the potassium conductance although in high concentrations the compound might also reduce Ca2+ influx through the cell membrane, which would contribute to an obvious negative chronotropic action. 1990 Royal Pharmaceutical Society of Great Britain