The site of action of furosemide

To establish whether furosemide (F) acts on the proximal tubule beside the thick ascending limb of Henle's loop, we reviewed the data from 55 rats studied before and during the i.v. infusion of 10 mg kg^-1 of furosemide. These animals were the object of previously published studies. SNGFR was 42.6 ± 1.1 nl min^-1 during baseline conditions (B), 42.7 nl min^-1 during F (P > 0.9). In 151 paired last proximal tubular samples, percentage reabsorption was 71.72 before and 71.72% after F (P = 1.0). In 64 paired early distal tubular samples, percent reabsorption fell from 86% in B to 78% during F (P < 0.0001). During F, the urine flow rate expressed as a percentage of GFR (24 ± 2%) was significantly correlated (R = 0.52, P < 0.0001) with the percent delivery of filtrate out of the proximal tubule (26 ± 3%). These data demonstrate that, even at this very high dosage, F does not act on the proximal tubule. It inhibits transport on the ascending limb of Henle's loop. By allowing the delivery of isotonic tubular fluid to the distal tubule, it causes a fall in volume absorption along the early distal convolution in proportion to its baseline water permeability. It increases urine flow by abolishing the interstitial hypertonicity and, consequently, the osmotically driven solvent flow across the distal epithelium and collecting ducts. Therefore the urine flow rate during F closely approximates volume delivery out of the proximal tubule.