Tachyphylaxis to ethacrynic acid in the isolated atrium of guinea-pig and its relation to noradrenaline stores.

1 The isolated electrically-paced atrium of the guinea-pig developed a dose-dependent increase in the force of contraction in response to ethacrynic acid (12-100 microgram/ml) which was blocked by pretreatment of the animals with reserpine but was unaffected by desipramine or colchicine added to the bathing medium. 2 There was a rapidly developing tachyphylaxis to repeated doses of ethacrynic acid which was not reversed by rest or incubation of the tissue with noradrenaline. 3 There was no cross tachyphylaxis between ethacrynic acid and tyramine, amphetamine or nicotine. 4 Ethacrynic acid (200 microgram/ml) decreased the noradrenaline content of the atria by 32%. 5 It is concluded that ethacrynic acid exerts its effects indirectly through the release of endogenous noradrenaline and that the mechanism of release seems to be different from that of other known indirect sympathomimetic drugs.