Amiloride: relationship between cardiac effects and inhibition of Na+/Ca2+ exchange.

The potassium sparing diuretic amiloride at concentrations ranging between 0.1-0.8 mM inhibited the Na+/Ca2+ exchange in sarcolemmal vesicles isolated from beef heart. The rate of exchange activity was 50% reduced by 0.35 mM amiloride. In spontaneously beating atria isolated from normal and reserpinized guinea-pigs, amiloride produced a concentration-dependent positive inotropic effect and negative chronotropic effect (EC50 = 0.7 mM). Amiloride protected spontaneously beating atria and left atria driven at 1 Hz from digitalis cardiotoxicity assessed in terms of a raised end-diastolic tension. It is suggested that the positive inotropic effect, negative chronotropic effect of amiloride and heart protection against digitalis toxicity are related to the observed inhibition of sarcolemmal Na+/Ca2+ exchange activity.