“Supramaximal” enhancement of the inotropic effect of noradrenaline by tyramine

Summary The positive inotropic effect of noradrenaline on the guinea-pig papillary muscle is potentiated in the presence of 1×10^–5 M tyramine, the concentration of noradrenaline that is necessary to produce a half maximal increase in force of contraction being reduced to about one third. There is no alteration of the maximal inotropic effect since the concentration-effect curve of noradrenaline is simply shifted to the left.In the presence of 3×10^–3 M tyramine, which by itself increases contractility by a dual mechanism (an indirect sympathomimetic and a direct postsynaptic one which is not induced by stimulation of adrenergic -receptors), noradrenaline (1×10^–5 M) produces an additional inotropic effect leading to a force of contraction which surmounts the maximum of the normal concentration-effect curve of noradrenaline by about 30%.The supramaximal isometric contraction curve of the papillary muscle produced by the combined effects of 3×10^–3 M tyramine and 1×10^–5 M noradrenaline differs from the contraction curve in the presence of 1×10^–5 M noradrenaline alone in having a steeper ascending slope and a slower relaxation phase. The mean velocity of force development (S₁) exceeds the maximum value of the normal concentration-effect curve of noradrenaline by about 50%. There is no increase in the maximum of the mean velocity of relaxation (S₂).The relaxation time of the supramaximal contraction curve as well as the duration of its action potential are the result of the opposing influences of the two substances, noradrenaline shortening and tyramine prolonging both action potential and relaxation time.