The Site of Action of Furosemide and Other Sulfonamide Diuretics in the Dog*

The discovery of the countercurrent multiplier system as the mechanism responsible for the con-centration and dilution of the urine has provided a framework for the identification of the site of ac-tion of diuretic drugs. Agents that act at a single anatomic site in the nephron can be expected to alter the pattern of urine flow in a predictable way. A drug that acts solely in the proximal convoluted tubule, by causing the delivery of increased amounts of filtrate to the loop of Henle and the distal convolution, would augment the clearance of solute-free water (CH2o) during water diuresis and the reabsorption of solute-free water (TCHO) during water restriction. In contrast, drugs that inhibit sodium reabsorption in Henle's loop would impair both CHSo and TCHO. Finally, drugs that act only in the distal tubule would reduce CHSo but not TcH2o (1). It is possible, however, that a diuretic drug might inhibit sodium reabsorption at multiple sites. Under such circumstances, localization of the areas of the nephron where the drug acts is far more difficult, since the effects of action in one segment might alter or obscure the effects on another. A new sulfonamide diuretic, furosemide, 4- chloro-N- (2-furylmethyl)-5-sulfonylanthranilic acid (2), offers several advantages in the study of localization of action: a) it is extremely potent, and therefore produces large effects; and b) its duration of action is brief, thereby facilitating mul-tiple studies during a single experiment. A study