Effect of reserpine pretreatment on guinea pig ventricular performance and responsiveness to inotropic agents

Demonstration of reserpine-induced inotropic supersensitivity depends on such variables as the dose and time course of reserpine pretreatment, the species, the agonist being tested, the experimental preparation, the frequency of stimulation and possible cardiotoxic effects of reserpine. We therefore carried out a systematic investigation of the effects of reserpine pretreatment on the performance and responsiveness of working guinea-p]ig hearts to a variety of inotropic agents at different frequencies of stimulation. Preliminary studies of three pretreatment schedules showed that one dose of reserpine (2.5 mg/kg/day for 2 days) increased left ventricular performance by vertically displacing the pressure-work curve (37 degrees C,. 250 beats/min). This dose of reserpine had no effect on coronary vascular resistance. The increase in performance was interrelated with an inotropic supersensitivity to calcium, characterized by an increase in +dP/dt, left ventricular pulse pressure and stroke work at calcium concentrations ranging from 1.0 to 4.0 mM, without a change in estimated pD2 values for calcium. The supersensitivity to calcium was frequency-dependent; it was present at 250 beats/min, but absent at frequencies of 275 beats/min or higher. Reserpine pretreatment increased the inotropic potency (pD2) of dl-isoproterenol (beta), but had no effect on the potencies of histamine (H2), phenylephrine (alpha) or pyridylethylamine (H1). The results show that reserpine pretreatment (2.5 mg/kg/day, 2 days) selectively increased the inotropic responsiveness of working guinea-pig hearts to calcium and to isoproterenol. They further suggest that the mechanisms for these two effects of reserpine are probably different.