Effects of guanabenz acetate on the pacemaker activity of rabbit sinoatrial node cells

The effects of guanabenz acetate on the electrophysiological properties of isolated rabbit sinoatrial node were studied using conventional microelectrode and double-microelectrode voltage clamp methods and were compared with those of clonidine and guanethidine. In spontaneously beating sinoatrial node preparations, guanabenz decreased the heart rate, the maximum rate of rise (Vmax), the action potential amplitude and the rate of diastolic depolarization in a dose-dependent fashion, whereas the action potential duration at 50% repolarization was prolonged. In comparison with clonidine and guanethidine, the inhibitory potency of guanethidine on the heart rate is weaker than that of guanabenz and clonidine. On the current systems, the voltage clamp experiments showed that guanabenz reduced the slow inward current and the time-dependent potassium outward current. These observations indicate that guanabenz acts directly on cardiac tissues and its bradycardic action can be mainly explained by a reduction of delayed current systems.