Loop diuretics reduce lithium reabsorption without affecting bicarbonate and phosphate reabsorption

The effects of the loop diuretics ethacrynic acid and bumetanide on lithium, bicarbonate and phosphate reabsorption were compared in 16 anaesthetized, normovolaemic dogs. In six dogs, ethacrynic acid (3 mg kg-1 body wt) significantly reduced absolute lithium reabsorption from 29.3 +/- 4.1 to 19.0 +/- 3.4 mumol min-1, fractional lithium reabsorption from 0.65 +/- 0.04 to 0.37 +/- 0.04 and fractional chloride reabsorption from 1.00 +/- 0.00 to 0.65 +/- 0.02. Bicarbonate and phosphate reabsorption did not decrease significantly. In six other dogs, bumetanide (30 micrograms kg-1 body wt) gave similar results. Absolute lithium reabsorption significantly decreased from 34.0 +/- 2.2 to 18.1 +/- 2.6 mumol min-1 and fractional lithium reabsorption decreased from 0.50 +/- 0.03 to 0.25 +/- 0.03. Fractional chloride reabsorption decreased from 0.98 +/- 0.00 to 0.61 +/- 0.05, whereas bicarbonate and phosphate reabsorption were not significantly altered. Thus, both loop diuretics greatly reduced lithium reabsorption. We propose that loop diuretics inhibit passive lithium reabsorption in the thick ascending limb of Henle's loop by reducing the lumen-positive electrical potential that drives passive cation transport.