Amiloride inhibits proximal tubular reabsorption in conscious euvolemic rats.
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 x kg(-1) x 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.
Thomsen
Klaus
K
Institute for Basic Psychiatric Research, Department of Biological Psychiatry, Aarhus University Hospital, Skovagervej 2, DK-8240 Risskov, Aarhus, Denmark. klausth@post6.tele.dk
Jonassen
Thomas E N
TE
Christensen
Sten
S
Shirley
David G
DG
D000042:Absorption / Q000187:drug effects; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D003243:Consciousness; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008094:Lithium / Q000652:urine; D009399:Nephrons / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000652:urine; D013047:Specific Pathogen-Free Organisms; D014882:Water-Electrolyte Balance / Q000187:drug effects
D004232:Diuretics; D000584:Amiloride; D008094:Lithium; D012964:Sodium; D011188:Potassium