THE EFFECT OF ETHACRYNIC ACID ON THE GUINEA‐PIG AND RAT ISOLATED VAS DEFERENS

1 The effect of ethacrynic acid (EA) was studied on guinea‐pig and rat vas deferens in vitro. 2 EA contracted the guinea‐pig but not the rat vas deferens in a dose‐dependent manner (50–800 μg/ml). Tyramine caused contraction in 10 out of 18 guinea‐pig vas deferens; EA caused contraction in 17 of the preparations which did not respond to tyramine. Repeated doses of EA produced tachyphylaxis, but there was no cross tachyphylaxis to tyramine. 3 The contractions produced by EA were prevented by phentolamine or reserpine pretreatment and potentiated by cocaine. A low concentration of desipramine (3 ng/ml) potentiated and higher concentrations (0.6 and 3.0 μg/ml) inhibited the response of vas deferens to EA. 4 Hexamethonium (100 μg/ml) or atropine (0.1 μg/ml) did not inhibit the effect of EA, excluding the nicotinic and muscarinic receptors as the sites of action. 5 The effect of noradrenaline (NA) on the guinea‐pig and rat vas deferens was enhanced by EA pretreatment, which may be due to inhibition of NA uptake. 6 It is concluded that EA releases NA from guinea‐pig vas deferens. The mechanism of release seems to be different from that of tyramine.