Electrophysiological effects mediated by the stimulation of cardiac β2-adrenoceptors with tulobuterol

We studied the electrophysiological effects of the specific beta 2-agonist tulobuterol in the guinea-pig sinus node and in sheep cardiac Purkinje fibers. Stimulation of beta 2-adrenoceptors by tulobuterol resulted in a slight increase in the rate of firing of the sinus node. In Purkinje fibers, however, automaticity was not affected up to concentrations of 10(-6) M. Consistently, tulobuterol (10(-8)-10(-6) M) did not affect the pacemaker current studied under voltage-clamp conditions. In the same range of concentrations (10(-8)-10(-6)M) tulobuterol dose-dependently increased the contractile force of driven Purkinje fibers. Tulobuterol, at a very high concentration (10(-5) M), had membrane depressant effects as demonstrated by the block of automaticity induced in the spontaneously beating Purkinje fibers and by the reduction of the maximum rate of depolarization in driven preparations. Our results suggest that stimulation of beta 2-adrenoceptors with tulobuterol in sheep Purkinje fibers is associated with an inotropic rather than a chronotropic effect. On the whole, the data confirm the lack of cardiac side effects of tulobuterol.