The mechanism of the antipolyuric action of amiloride in lithium- treated rats

Polyuria is a frequent complication in lithium-treated patients. Amiloride, a potassium sparing diuretic was shown to improve the polyuric effect of lithium in both experimental animals and men. However, the mechanism of this action is debated. In this study, we aimed to differentiate between the two possible mechanisms of this action which were previously suggested by different authors. In lithium-treated rats with severe polyuria, amiloride administration (1.2 mg/kg/day intraperitoneally, for 1 week) decreased the mean urine volume significantly from a mean of 147.5 ± 16.1 ml/day to 51.7 ± 4.75 ml/day (p < 0.05). In this dosage amiloride also decreased the urinary potassium excretion from a mean of 4.01 ± 0.36 mmol/day to 2.49 ± 0.39 mmol/day (p < 0.05) with no significant changes in urinary sodium and lithium excretions. There were no significant changes in plasma Na+, K+ and Li+ levels after amiloride consumption. Amiloride also had a protective effect when administered prior to lithium. These results suggest that the effect of amiloride is due to a direct action on distal tubular cells rather than to volume depletion as is seen after thiazide administration.