Summary
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1.
The positive inotropic effect of dihydroouabain in the isolated guinea-pig papillary muscle was studied in dependence on frequency of contraction and on extracellular calcium concentration.
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2.
Reduction of contraction frequency from 1 Hz to 1/300 Hz at a calcium concentration of 3.2 mM led to a decrease in inotropic efficiency of the glycoside as evidenced by a marked shift of its concentration-effect curve. A concentration of 5×10−5 M dihydroouabain which was, on the average, maximally effective at 1 Hz contraction frequency was practically ineffective when the muscles contracted only once every 5 min.
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3.
Reduction of [Ca2+]0 from 3.2 mM to 0.6 mM at a contraction frequency of 1 Hz led only to a shift of the glycoside concentration-effect curve on the vertical axis according to the decrease in control force of contraction.
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4.
The different parameters of the isometric contraction curve (steepness of the ascending and descending limb, S1 and S2; time to peak force, t1, and relaxation time, t2) were equally affected in relation to peak force of contraction (Fc) by changes in contraction frequency in absence and in presence of different concentrations of dihydro-ouabain. In contrast, the time parameters t1 and t2 were differently influenced by a change in [Ca2+]0.
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5.
The results are consistent with the hypothesis of the inhibition of the cellular sodium pump by cardioactive steroids as the cause of their positive inotropic effect on the heart.
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Ebner, F., Reiter, M. The dependence on contraction frequency of the positive inotropic effect of dihydro-ouabain. Naunyn-Schmiedeberg's Arch. Pharmacol. 300, 1–9 (1977). https://doi.org/10.1007/BF00505073
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DOI: https://doi.org/10.1007/BF00505073