EFFECT OF AMILORIDE ON INOTROPIC AND TOXIC ACTIONS OF OUABAIN IN GUINEA-PIG LEFT ATRIA

The effect of amiloride on the positive inotropic and toxic effects of ouabain in guinea-pig left atria has been studied. In atria driven at 1 Hz, amiloride (0.3 and 0.5 mM) decreased the EC(50) but did not aff ect the maximal tension developed by ouabain. At 0.1 Hz, amiloride did not change either the EC(50) or the maximal tension developed by ouab ain. Ouabain toxicity (onset of arrhythmias) was not changed by amilor ide at either frequency of stimulation. Therefore, amiloride did not a ntagonize either the positive inotropic or the toxic effect of ouabain . The positive inotropic effect of amiloride has been ascribed to the inhibition of the Na+/Ca2+ exchanger. Since amiloride inhibits also th e Na+/H+ exchanger, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an amilor ide derivative which selectively inhibits the Na+/H+ exchange, has bee n tested to evaluate the role of the Na+/H+ exchange in the amiloride- ouabain interaction. EIPA increased the EC(50) values of ouabain and d ecreased the maximal developed tension by the glycoside in atria drive n at 0.1 and 1 Hz, but did not antagonize the toxic response (arrhythm ias) of atria to ouabain. It is suggested that the inhibition of Ca2exit through the Na+/Ca2+ exchange by amiloride and ouabain may explai n the observation that the positive inotropic effects of amiloride and ouabain are additive.