Independence of the positive inotropic effect of ouabain from the inhibition of the heart Na+/K+ pump.

Abstract

Isolated left atria from guinea pigs were stimulated at 3.3 Hz and bathed at 30.degree. C in Tyrode''s solution containing 6 mM KCl. After equilibration, this solution was replaced by a low-K solution or by Tyrode''s solution containing ouabain or dihydroouabain. The treatments evoked an increase in the contractility of the atria. The time to peak increase was .apprx. 30 min, and the inotropic effect was sustained for at least 40 min. After 30 min, 42K was added to the bathing solution to estimate the activity of the Na+/K+ pump. A linear relationship was observed between the degree of inhibition of the Na+/K+ pump and the increase in systolic tension. The regression line was the same for low-K solutions and dihydroouabain but not for ouabain. For a given degree of inhibition of the pump, ouabain evoked a higher increase in contractility. Inhibition of the Na+/K+ pump can be the only mechanism responsible for the positive inotropic effect of dihydroouabain but cannot be the sole mechanism for that of ouabain.