Negative inotropic effect of beta-blockers in the guinea-pig atrium after preincubation with isoprenaline.

In the isolated guinea-pig atrium, pretreated with a high concentration of isoprenaline (8 x 10(-7) M), beta-blockers produced a marked negative inotropic effect in a concentration which by itself was too low to have a direct depressing action. No negative inotropic effect was caused by isoprenaline when beta-blockers were applied first. The depressing action of beta-blockers was unaffected by phentolamine or atropine. During the depression, the electrical parameters of the action potential were not significantly different from those of the control, though the contractions were much smaller than control ones. The negative inotropic effect of beta-blockers was weaker in excess Ca (7.5--10 mM). The observations indicate that isoprenaline possesses a dual action but that the negative inotropic effect is usually masked by the positive inotropic effect and that beta-blockers, by quickly abolishing the positive inotropic effect, reveal the underlying negative inotropic effect.