Analysis of the inotropic action of ouabain in rat ventricles: two apparent ouabain inotropic responses.

Two distinct inotropic effects of ouabain were observed in 68 of 82 right ventricular strips of rats with ED50s of 0.5 and 20 microM referred to as "low-dose" and "high-dose" effects, respectively. The other 14 strips showed monophasic dose-response curves, with an apparent ED50 of 0.3 microM; the inotropic response to ouabain or isoproterenol developed by these atypical strips did not exceed 50% over control. In the strips showing the biphasic inotropic response curves, the proportion of the "low-dose" effect varied from 6 to 89% of the maximum response. After treatment with 160 microM ouabain, followed by 60 min of washout, the maximum developed tension in response to ouabain was unchanged, but the "low-dose" effect was abolished or dramatically reduced. In those cases with a remaining "low-dose" response, the response was only 12% or less of the maximum and the ED50 was shifted from 0.3 to about 3 microM ouabain by the washout. The atypical strips, which showed only the "low-dose" effects during the first ouabain exposure, revealed after washout a consistent "high-dose" effect with an ED50 of about 12 microM ouabain. The data show that the two inotropic responses exist in all ventricular strips and that in some strips, after ouabain washout, a residue of the "low-dose" effect remains.