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TACHYPHYLAXIS TO ETHACRYNIC ACID IN THE ISOLATED ATRIUM OF GUINEA‐PIG AND ITS RELATION TO NORADRENALINE STORES
Author(s) -
KHOYI M.A.,
POUSTI A.,
POWIS G.,
ZARRINDAST M.R.
Publication year - 1978
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1978.tb07789.x
Subject(s) - tachyphylaxis , guinea pig , atrium (architecture) , sympatholytics , pharmacology , chemistry , medicine , atrial fibrillation
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 μg/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 μg/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.