Abstract

Free water clearances, stop-flow and retrograde intraluminal infusion techniques were used to identify the renal site of action of Su-15049, an arylcyclohexanone derivative that increases the renal excretion of sodium but not the excretion of potassium. During water diuresis, Su-15049 increased urine volume and the clearance of solute-free water in anesthetized dogs. There was little change in sodium excretion, osmolar clearance, or the clearance of inulin. During the i.v. infusion of Su-15049, the proximal limb of the sodium stop-flow pattern was significantly elevated and there was a concomitant decrease in the maximal inulin urine/plasma ratio. The distal limb of the pattern was not altered significantly. The effects of Su-15049 on the distal potassium stop-flow pattern were variable. When the drug was infused retrogradely through a catheter placed in the renal pelvis, a marked reduction in the excretion of potassium was observed. Our data indicate that the proximal tubule is a primary site of the natriuretic action of Su-15049. However, an effect on the distal tubular transport of sodium cannot be excluded. The potassium-sparing action of the drug is a result of enhanced distal tubular reabsorption of the ion.