Effects of inotropic agents on isolated guinea pig heart under conditions that modify calcium pools involved in contractile activation

Abstract

Positive inotropic effects of strophanthidin were compared with those of isoproterenol, BAY K 8644, grayanotoxin, veratridine, and monensin in electrically stimulated left atrial muscle preparations of guinea pig heart under conditions in which the calcium pool, playing a primary role in contractile activation, was altered. In concentrations that caused similar degrees of increase in developed tension under 1 Hz stimulation, grayanotoxin and strophanthidin caused a relatively large increase in potentiated postrest contraction compared with that caused by isoproterenol, whereas the effect of BAY K 8644 on the postrest contraction was the smallest. The effect of high concentrations of grayanotoxin or strophanthidin, however, resembled that of isoproterenol. The sensitivity of the isolated heart muscle to these agents was compared under conditions in which utilization of various calcium pools contributing to contractile activation was suppressed. Mn2+, which reduces contribution of very superficial Ca2+, reduced sensitivity of heart muscle to the positive inotropic effect of isoproterenol and enhanced the inotropic effect of monensin or veratridine. Verapamil, nifedipine, diltiazem, or ryanodine did not have marked effects on the positive inotropic action of Ca2+, monensin, veratridine, or strophanthidin. These results suggest that the positive inotropic actions of veratridine, grayanotoxin, and strophanthidin share a common mechanism and that low concentrations of strophanthidin may increase loading of Ca2+ pool, which plays an important role in potentiated postrest contraction.