Micropuncture study of the effect of furosemide on proximal and distal tubules of the rat nephron

The tubular effects of furosemide were studied by micropuncture and clearance techniques on 20 rats. Collections of tubular fluid (TF) from early distal (ED) and late proximal (LP) segments of the same nephrons and of different nephrons were performed during baseline conditions. Re-collection were taken from the same sites and new collections from different nephrons after 10 mg/kg furosemide. The glomerular filtration rate (GFR) was 1,309 ± 212 μl/min during baseline, and 1,348 ± 199 μl/min after furosemide (p > 0.89); while the urine flow rate rose from 36 ± 8 to 167 ± 30 μl/min (p < 0.001). The nephron filtration rate (NFR) was not different in 46 paired distal (33.3 ± 2.6 nl/min) versus proximal samples (34.2 ± 2.9 nl/min, p > 0.72), neither was it different during baseline (37.2 ± 1.4, n = 120) as compared to furosemide (37.2 ± 2.7, n = 91, p > 0.99). The percent reabsorption (PR) at the ED sampling site was 87 ± 4% during baseline, and 89 ± 3% in 13 paired samples during furosemide (p > 0.47). PR at the LP sampling sites was 83 ± 2% during baseline, and 80 ± 2% in 26 paired samples during furosemide (p > 0.63). In 31 paired ED-LP collections, PR was 82 ± 4 (ED) versus 72 ± 4% (LP) during baseline, and 87 ± 3 versus 74 ± 6%, respectively, during furosemide. The respective collection rates were 4.6 ± 1.0 versus 9.5 ± 1.3 nl/min during baseline (p<0.0001), 5.8 ± 2.3 versus 8.7 ± 3.0 nl/min during furosemide. The LP-ED differences obtained during baseline were not different from those measured during furosemide for the collection rate, PR and NFRs. The absolute LP resorption rate was not significantly different during baseline as compared to furosemide. Thus, furosemide did not affect the difference between ED and LP collection sites in collection rate, absolute and fractional reabsorption, in the absence of changes in GFR and NFR. These data indicate that furosemide acts solely along Henle's loop, where it blocks Na⁺ transport. The urine flow rate rises during furosemide because water abstraction along the distal tubule is reduced by the isotonicity of ED TF, and along the collecting duels by the isotonicity of the medullary and papillary interstitium caused by the diuretic. We conclude that under the conditions of the present study, furosemide has no proximal effect.