Inhibition of tubular lithium reabsorption by amiloride in the conscious sodium-restricted rat.
We examined the effects of amiloride administration on the renal lithium clearance (CLi) in three series of conscious, unrestrained rats maintained on either a low (5 mmol/kg) or normal (200 mmol/kg) sodium diet. In series 1, six doses of amiloride (0.5-16 mg/kg) were administered s.c., and the renal electrolyte excretion was assessed over a 3-h clearance period. In series 2, the time profile of changes in renal electrolyte excretion following 4 mg/kg of amiloride s.c. was examined, and in series 3, the effect of amiloride infusion i.v. (1 mg/kg followed by 2 mg/kg per h) on renal function was investigated. In all series CLi was lower in sodium-restricted rats than in controls. Amiloride administered s.c. to sodium-restricted rats did not increase the 3-h CLi to the levels found in control rats. When amiloride was administered s.c. or i.v. and urine collected in 30-minute periods, CLi in rats fed a sodium-deficient diet increased to control levels. We conclude that amiloride-induced losses of sodium and water in CLi studies may lead to an erroneous interpretation of data. However, distal tubular lithium reabsorption may be recognized, if present, by the administration of amiloride i.v. or s.c. during collections of urine in short time intervals.
Shalmi
M
M
Department of Pharmacology, University of Copenhagen, Denmark.
Thomsen
K
K
D000042:Absorption; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D003864:Depression, Chemical; D004039:Diet, Sodium-Restricted; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D008094:Lithium / Q000493:pharmacokinetics*; D008297:Male; D011188:Potassium / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000652:urine
D000584:Amiloride; D008094:Lithium; D012964:Sodium; D011188:Potassium