Effect of ouabain on the renal response to furosemide

The aim of this work was to investigate whether the natriuretic effect of furosemide can be wholly explained by the inhibition of a ouabain-sensitive Cl transport in the thick ascending limb of Henle. For this purpose 6 dogs undergoing moderate saline diuresis received 100 mug ouabain/kg into the left renal artery followed by 2 mg furosemide/kg IV. Urine was collected from both kidneys and blood samples taken at regular intervals. Ouabain produced a unilateral increase in Na excretion and little change in CCR and water and K excretion. IV furosemide increased Na, K and water excretion in both kidneys. Since Na excretion in the left kidney was already exhanced by ouabain the increment was lesser than in the right kidney. As a result water and electrolyte excretion became similar in both kidneys. Although ouabain did not prevent the renal response to furosemide, the effects of both drugs were not additive. This suggests that in addition to the thick ascending limb, furosemide acts in some other tubular segment which is insensitive to ouabain. Since furosemide is known to also inhibit passive Cl movements, a second site of action could be in the thin ascending limb of Henle, which lacks any active transport mechanism but is highly permeable to Cl.