Effects of chronic reserpine pretreatment on myocardial sodium pump and inotropic sensitivity to ouabain in guinea pig heart

The effects of chronic reserpine pretreatment (0.1 mg/kg/day, 7–9 days) on myocardial sodium pump activity, the binding of ³H-ouabain to Na⁺, K⁺-ATPase, and the positive inotropic effect of ouabain were studied in guinea pig hearts. Ouabain-sensitive ⁸⁶Rb uptake, an estimate of sodium pump activity, was significantly decreased (33.0%) in papillary muscles of chronic reserpine-pretreated guinea pigs as compared to the saline-treated controls. Kinetic analyses of the interaction of ³H-ouabain with Na⁺, K⁺-ATPase indicated that chronic reserpine pretreatment resulted in a significant decrease (24.3%) in the maximum ³H-ouabain binding site concentration when the results were expressed as pmoles per mg protein. The maximum ³H-ouabain binding sites or the number of Na⁺, K⁺-ATPase units, however, were not significantly different between the two groups when they were expressed as pmoles per mg DNA. The affinity or the dissociation rate constant (Kd) of ³H-ouabain binding was not altered after chronic reserpine pretreatment. In isolated, electrically-driven left atrial preparations, the basal contractile force was slightly higher in the reserpine-pretreated animals; the subsequent development of the positive inotropic effect and the concentration of ouabain needed to produce half-maximal inotropic response, however, were not different from the controls. Thus, it is concluded that chronic reserpine pretreatment is accompanied by a significant reduction in myocardial sodium pump activity; however, the number of sodium pump sites per cell was unchanged. The sensitivity of the reserpine-pretreated myocardium to the inotropic action of ouabain as well as its affinity for ³H-ouabain binding $\text{in vitro}$ are also unchanged.