THE NEGATIVE INOTROPIC ACTION OF NOREPINE-PHRINE IN THE PRESENCE OF OUABAIN

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Cotten and Cooper (1) showed that cardiac glycosides blocked the positive inotropic response to norepinephrine (NE) in the dog heart during hypothermia. The principal cause of its negative inotropic response to NE has been studied by some investigators. The negative inotropic response to NE is primarily the result of a decrease in the velocity of cardiac contraction (2) and its occurrence is related to the maximum plasma level of NE. The contractile force increased until the estimated plasma concentrations of NE reached 8 to 10 mμg/ml and decreased at higher concentrations. The glycosides apparently inhibited the uptake of NE by the heart (3).
More detailed analyses have been performed with isolated heart preparations. The production of the negative inotropic response to NE was observed only after ouabain was given at 27°C, but ouabain had no significant effect on the contractile response to NE at 37°C in isolated guinea-pig hearts (4). On the other hand, Godfraind and Godfraind-De Becker (5), who tested the response to NE in isolated spontaneously beating guinea-pig atria treated with ouabain, noted that the negative inotropic action of NE was more marked with high concentrations or at high temperature of 37°C. They supposed that the negative inotropic response to NE was related to the toxic phase of ouabain.
The present study was designed to investigate the mechanism of the negative inotropic response to NE after ouabain.