Mugelli A, Amerini S, De Bonfioli Cavalcabo P, Cerbai E, Visentin S
Institute of Pharmacology, University of Ferrara, Department of Preclinical and Clinical Pharmacology, Italy.
Cardiovasc Drugs Ther. 1987;1(1):101-7. doi: 10.1007/BF02125839.
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.
我们研究了特异性β2-激动剂妥洛特罗对豚鼠窦房结和绵羊心脏浦肯野纤维的电生理作用。妥洛特罗刺激β2-肾上腺素能受体导致窦房结放电频率略有增加。然而，在浦肯野纤维中，浓度高达10(-6) M时自律性并未受到影响。同样，妥洛特罗（10(-8)-10(-6) M）在电压钳制条件下不影响所研究的起搏电流。在相同浓度范围内（10(-8)-10(-6)M），妥洛特罗剂量依赖性地增加了受驱动的浦肯野纤维的收缩力。在非常高的浓度（10(-5) M）下，妥洛特罗具有膜抑制作用，这表现为自发性搏动的浦肯野纤维中诱导的自律性受到阻断以及受驱动制剂中最大去极化速率降低。我们的结果表明，在绵羊浦肯野纤维中用妥洛特罗刺激β2-肾上腺素能受体与变力作用而非变时作用相关。总体而言，数据证实了妥洛特罗无心脏副作用。
