Effect of frusemide on lithium clearance and proximal tubular reabsorption in anaesthetized rats

1. In order to investigate the lithiuretic effect of frusemide, simultaneous measurements of fractional lithium excretion (FELi) and fractional fluid delivery to the end of the proximal convoluted tubules were made in Inactin-anaesthetized rats, first during a control period, then during intravenous infusion of frusemide at either 0.8 or 8.0 mg kg-1 h-1. Fluid balance was maintained by infusion of NaCl-KCl solution adjusted to match urinary excretion rates; measurements were made after urine flow had stabilized. 2. In time-control animals, which did not receive frusemide, no significant changes were observed in either FELi or fractional fluid delivery to the end of the proximal convoluted tubules (determined as the plasma/tubular fluid inulin concentration ratio, P/TFIn). 3. In animals given the high dose of frusemide, FELi increased from 0.22 +/- 0.02 (mean +/- S.E.M.) during the control period to 0.45 +/- 0.03 during frusemide infusion (P less than 0.001); this was accompanied by a modest increase in P/TFIn, from 0.43 +/- 0.02 to 0.51 +/- 0.02 (P less than 0.01). 4. In animals given the lower dose of frusemide, FELi increased from 0.21 +/- 0.01 to 0.37 +/- 0.01 (P less than 0.001). In this group, however, there was no discernible change in P/TFIn (0.43 +/- 0.02 vs. 0.44 +/- 0.01, not significant). 5. These results suggest that under control conditions a significant component of lithium reabsorption may occur beyond the proximal tubule, most likely in the loop of Henle.