A concentration-dependent biphasic positive inotropic action of ouabain on isolated heart of rat and guinea-pig.

Log dose-response curves of ouabain on rat and guinea-pig heart revealed the existence of a concentration-dependent, biphasic inotropic effect of ouabain. With rat as with guinea pig heart the "first" effect observed at the lowest concentrations of ouabain, was relatively small (rat: 115% of control, at 10(-6) M ouabain; guinea-pig: 110% of control, at 6.25.10(-10) M ouabain) but statistically highly significant (p less than or equal to 0.001). The shape of the concentration-effect relationship for this first action differed between species. With rat heart it was sigmoid in character and had a flat slope, with guinea-pig on the contrary it was almost bell-shaped (i.e. the effect disappeared with increasing ouabain concentration). The shape of the concentration-effect relationship for the "second" action was sigmoid in shape for both species used (rat: between 10(-6) - 10(-4) M; guinea-pig: between 10(-8) - 10(-6) M ouabain). From the results is was concluded that the dual positive inotropic effect of ouabain supports the existence of at least two different mechanisms of action of this drug. Furthermore, it was suggested that a species-dependent binding of calcium to the cardiac sarcolemma may be responsible for the different shapes of the "first" positive inotropic effect of ouabain.