RENAL SITES OF ACTION OF ETHACRYNIC ACID

¹ Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

Evidence for the existence of a proximal tubular site of action of the diuretic, ethacrynic acid, was collated in several series of experiments. The major objective of the experiments was to control renal distribution of the drug so that pharmacologically effective concentrations occurred, for a finite period of time, only in cells or cellular membranes of the proximal tubule. This was achieved in anesthetized dogs by occluding one ureter just before injecting ethacrynic acid (modified stop-flow procedure). The proximal limb of stop-flow urine derived from this preoccluded side contained higher concentrations of Na, Cl and K and there was virtually no ethacrynic acid or metabolite of the compound (C¹⁴ activity) in urine derived from distal segments; in contrast, large amounts of C¹⁴ activity were found in samples from distal segments and the stop-flow concentrations of Na and Cl were elevated throughout the pattern in samples taken from the contralateral (nonpreoccluded) side. Counter-experiments, in which renal distribution and concentration of ethacrynic acid were controlled by other means (e.g., use of small doses, infusions of probenecid, varying duration of occlusion), furnished data of a similar nature and supported the conclusion that the proximal tubule is one of the sites of action of ethacrynic acid.