ALTERATION BY PROPRANOLOL OF THE INOTROPIC AND BATHMOTROPIC EFFECTS OF DIHYDRO-OUABAIN ON GUINEA-PIG PAPILLARY-MUSCLE

1. The effect of dihydro-ouabain on the force of contraction and electrical excitability of the isolated guinea-pig papillary muscle was studied under the influence of (+)- and (±)-propranolol. 2. 10-5 and 4×10-5 mol/l of (+)- or (±)-propranolol had a negative inotropic effect. Both the racemate and the dextro isomer reduced the inotropic effectiveness of the glycoside to the same extent. These actions were not influenced by catecholamine depletion. Even at high concentrations of dihydro-ouabain, which cannot be investigated in the absence of propranolol due to a glycoside-induced automaticity of the muscles, endogenous catecholamines were not involved in the inotropic effect. 3. Dihydro-ouabain had a concentration-dependent negative bathmotropic effect; 8×10-5 mol/l increased the stimulation threshold by about eight percent. The negative bathmotropic action of dihydro-ouabain was enhanced by (+)- or (±)-propranolol, in addition to their own depressant effect on electrical excitability. 4. Due to the combined negative bathmotropic effects, an increasing number of muscles became in-excitable at high concentrations of the glycoside in the presence of 4×10-5 mol/l (±)-propranolol but not in the presence of the same concentration of (+)-propranolol. This difference suggests that dihydro-ouabain in high concentrations releases endogenous noradrenaline which increases excitability via β-adrenoceptors. © 1979 Springer-Verlag.