Effects of Ethacrynic Acid (a New Saluretic Agent) on Renal Diluting and Concentrating Mechanisms: Evidence for Site of Action in the Loop of Henle*

Ethacrynic acid (MK-595) 1 is a new orally ac- tive saluretic agent structurally unrelated to or- ganomercurial or benzothiadiazine diuretics (2). Its biological properties in experimental animals were first studied by Baer, Russo, Michaelson, and Beyer (3, 4), who reported it to be a natri- uretic drug more potent than chlorothiazide and suggested that it might have a novel mode of action. Clinically, its potency seems to be com- parable to parenterally administered organomer- curials, and it has been effective in patients previ- ously refractory to other diuretics (5, 6). Be- cause of the potential importance of this drug as an effective agent in the treatment of edema, the present study was undertaken to gain knowledge of the site or sites of action of the drug in the human kidney by determining its effects on urinary dilu- tion and concentration.