Effect of the alpha-adrenoceptor antagonist urapidil on the pacemaker activity of rabbit sino-atrial node preparations.

We studied the effects of the alpha-adrenoceptor antagonist urapidil on the sino-atrial node pacemaker activity of the rabbit. Urapidil (above 10 microM) decreased the spontaneous firing frequency and the maximum rate of rise of the action potential, and prolonged the action potential duration at half-amplitude. Above 100 microM, urapidil also reduced the rate of the diastolic depolarization and the action potential amplitude. On the current systems, urapidil depressed the slow inward current and the time-dependent potassium outward current. The hyperpolarization-activated inward current was also reduced with only a high concentration (300 microM). Furthermore, the agent decreased the current oscillations induced by elevating [Ca]o. It is concluded that urapidil depresses the sinoatrial node pacemaker activity, mainly due to a reduction of Ca2+ influx through the cell membrane and it also eliminates the excessive intracellular Ca2+ load of nodal cells.