Amiloride inhibits proximal tubular reabsorption in conscious euvolemic rats

Abstract

Based on the results of micropuncture studies, it is generally assumed that amiloride inhibits Na + (and Li +) reabsorption in the distal nephron, without affecting proximal tubular reabsorption. This is the basis for the use of amiloride to test for distal nephron Li + reabsorption. We have examined the validity of this assumption by administering amiloride in doses of 0, 0.02, 0.07, 0.2 and 2.0 mg kg −1 h −1 to conscious, chronically instrumented rats fed a diet with a normal Na + and K + content. Na + and water homeostasis was maintained by servo-controlled replacement in order to avoid any effect of volume depletion on proximal tubular reabsorption. The effects of the two highest doses of amiloride were also examined without Na + and water replacement. In the servo-controlled rats, the two highest doses of amiloride increased the fractional excretion of both Na + (FE Na) and Li + (FE Li), whereas the two lowest doses affected only FE Na. In the rats without servo-control, FE Li also rose in response to amiloride infusion, but the increase was significantly lower than that observed in the servo-controlled animals. Since distal Li + reabsorption is absent or negligible in rats fed a diet with a normal Na + and K + content, the large increase in FE Li following the highest doses of amiloride (15–18% of the filtered load in servo-controlled rats) indicates inhibition of proximal tubular reabsorption. We conclude that amiloride, in doses usually employed to detect distal Li + reabsorption, inhibits proximal tubular reabsorption in conscious euvolemic rats.