Effect of amiloride on isolated guinea-pig atrium

The effect of high concentrations (62.5-500 microgram/ml) of amiloride, a potassium sparing diuretic, was investigated in the isolated guinea-pig atrium. Amiloride decreased the frequency of contractions of the spontaneously beating right atrium in a time-dependent fashion. The inotropic effect of amiloride was frequency-dependent. It increased the peak developed tension of the electrically paced left atrium with 1 Hz stimulation. This was dose and time-dependent. Stimulation at 0.35 and 0.1 Hz resulted in no effect and a negative inotropic effect respectively. The effects of amiloride were not prevented by atropine, propranolol, phenoxybenzamine, metiamide, tetrodotoxin or by pretreatment of animals with reserpine. The positive inotropic effect (at 1 Hz) was inhibited by calcium antagonists verapamil or chlorpromazine. The negative inotropic effect (at 0.1 Hz) was prevented by doubling calcium concentration of the medium. Amiloride had no significant effect on sodium, potassium and calcium content of the tissue. It is concluded that high concentrations of amiloride decreases the frequency and changes the peak developed tension of the guinea-pig atrium possibly by decreasing sodium entry and altering the availability of calcium to the contractile elements.