Effects of Ethacrynic Acid on the Isolated Collecting Tubule

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Abstract
Effects of the diuretic ethacrynic acid on osmotic water permeability were investigated in the isolated perfused collecting tubule of the rabbit kidney. The base-line water permeability of the collecting tubule was not affected when the drug (10−4M) alone was added to the bathing medium. Vasopressin alone in the bathing medium (2, 5 μU/ml) elicited a significant increase in osmotic water absorption. With vasopressin kept in the bathing medium, the addition of 10−5M ethacrynic acid depressed the hydro-osmotic effect of vasopressin by 50%. This inhibitory effect of low concentrations of ethacrynic acid could be surmounted by high, supramaximal dosage levels of vasopressin. When 10−4M ethacrynic acid was added to the bathing medium before vasopressin, the hydro-osmotic effect of vasopressin and the diuretic in combination was insignificant. Dibutyryl adenosine 3′5′-monophosphate (10−4-10−2M) alone in the bathing medium significantly increased baseline osmotic water flow, mimicing the effect of antidiuretic hormone. When ethacrynic acid was added together with the nucleotide, the permeability remained at the same high level. Theophylline, like the nucleotide and vasopressin, produced a significant hydro-osmotic effect. The magnitude of this response was not affected by further addition of ethacrynic acid (10−4M). It was concluded that ethacrynic acid is an antagonist of antidiuretic hormone. The antagonism probably occurs at the level of the receptor site of the hormone on the peritubular membrane. Antagonism to circulating antidiuretic hormone may therefore be one of the factors involved in the loss of renal concentrating ability brought about by ethacrynic acid diuresis.