Renal Tubular Effects of Ethacrynic Acid*

Abstract

Ethacrynic acid was administered intravenously to dogs during hydropenia with vasopressin infusion and during maximal water diuresis. The diuretic effect of the drug began within 2 minutes, and peak natriuresis occurred within 20 minutes. K+ excretion increased, and Cl- excretion approached the sum of cation excretion. The agent had a natriuretic potency 3 to 4 times that of chlorothiazide, with an average maximal effect resulting in the excretion of 17% of the filtered Na+. Renal concentrating ability was virtually abolished by ethacrynic acid. During water diuresis, the drug uniformly reduced, but did not eliminate, free water clearance. The addition of chlorothiazide always resulted in a further decrease in free water clearance. The two agents were additive in decreasing free water clearance and increasing solute excretion, regardless of the sequence of administration. These data are consistent with the premise that two drug-sensitive sites of urinary dilution exist. The loop of Henle, where electrolyte transport is common to both urinary dilution and concentration, is affected by ethacrynic acid and probably not by chlorothiazide. A more distal site of urinary dilution, not directly involved in the concentrating mechanism, may be affected by chlorothiazide and probably not by ethacrynic acid.