Sites of action of tripamide

Tripamide is a new diuretic derived from a sulfonamide nucleus that has both antihypertensive and natriuretic properties. We assessed its renal site of effect with standard clearance techniques. Studies during water loading indicated a 47% increase in fractional free water clearance (an effect opposite that of thiazide diuretics) and a simultaneous 75% increase in fractional delivery of solute to the diluting segment. Consequently, when free water clearance was assessed relative to delivery of solute, tripamide induced a decrease from 0.86 +/- 0.03 to 0.75 +/- 0.01. This indicated an inhibitory effect on solute reabsorption at the cortical segment of the thick ascending limb of Henle's loop. Studies during hydropenia indicated increased free water reabsorption. When factored for delivery of solute, however, free water reabsorption decreased from 0.66 +/- 0.02 to 0.61 +/- 0.02, indicating a site of effect of tripamide at the medullary segment of the thick ascending limb of Henle's loop. Tripamide also increased calcium excretion. No effects on renal hemodynamics or indices of effect at the proximal tubule were observed. The data indicate that tripamide is a loop diuretic that may also affect more proximal nephron sites.