CARDIOPROTECTIVE EFFECTS OF NISOLDIPINE - AN EXPERIMENTAL-STUDY ON GUINEA-PIG PAPILLARY-MUSCLE

It has been shown that dihydropyridines exert a cardioprotective effec t during experimental ischemia. This effect is reflected in a reduced K-efflux from the ischemic tissue. Recently we have shown that ischemi c K-efflux is largely mediated by ATP-dependent K-channels. Using K-se lective microelectrodes we studied the effect of nisoldipine on K-effl ux during simulated ischemia (guinea pig papillary muscle immersed in paraffin oil; normal Tyrode solution, HEPES buffered, 100% O-2-equilib rated, 37 degrees C). While ischemic K-efflux was Ca-dependent in stim ulated preparations, it was independent of extracellular Ca in resting preparations. Our results show that nisoldipine leads to an inhibitio n of ischemic K-efflux during simulated ischemia. In resting preparati ons this inhibition is not a direct Ca-antagonistic effect, since with drawal of extracellular Ca does not inhibit ischemic K-efflux but niso ldipine does. We suggest a direct effect of nisoldipine on the K-ATP c hannel which is mainly responsible for ischemic K-loss.