Effect of a Sodium‐Poor Diet on Lithium Clearance at Different Dietary Potassium Contents in Rats

Abstract

In rats on a diet with a sodium content of 300 mmol/kg, lithium is reabsorbed exclusively in the proximal tubules, and lithium clearance (CLi) equals the proximal tubular fluid output (Vprox). In rats on a sodium-poor diet (5 mmol/kg), lithium is also reabsorbed in the distal nephron and CLi is therefore lower than Vprox. The present paper examines the reduction of CLi in response to a low sodium diet in Brattleboro rats with hereditary diabetes insipidus maintained on different dietary potassium contents. CLi was reduced by about 60 microliter/min./100 g body weight in response to a low sodium diet. The absolute reduction in CLi caused by low sodium diet was unaffected by an increase of CLi provoked by administration of potassium with the diet, and it was unaffected by variations of CLi which occurred spontaneously within each group. CLi was accordingly reduced by a constant absolute value rather than by a constant percentage. The reduction of CLi (60 microliter/min./100 g body weight) was equal to CLi in the group given a potassium-poor diet with a normal sodium content. In the low-sodium and low-potassium group CLi was reduced to almost zero. Using CLi as a measure of Vprox in the rats on a 300 mmol/kg sodium diet it is concluded that the absolute reduction of CLi in response to a sodium-poor diet is 1) unaffected by increase of Vprox produced by administration of potassium with the food,2) unaffected by spontaneous variations of Vprox, and 3) equal to Vprox in rats given a potassium-poor diet.

Renal tubular lithium reabsorption in potassium‐depleted rats

“…Several studies have demonstrated that in rats subjected to potassium depletion, both C Li and the fractional excretion of lithium (FE Li ) are considerably reduced (Shirley & Walter, 1986; Thomsen & Leyssac, 1987; Shirley, Zewde & Walter, 1990), which on the face of it suggests a reduction in end‐proximal fluid delivery. This conclusion is supported by the observation that in Brattleboro rats, which lack vasopressin, the reduction in C Li during potassium depletion is accompanied by a reduction in urine flow rate (Thomsen & Leyssac, 1987); in the absence of vasopressin, changes in urine flow rate are thought to reflect changes in fluid delivery from the proximal tubules (Shirley, Walter & Thomsen, 1983; Levinsky & Lieberthal, 1992). More direct evidence for a reduced end‐proximal fluid delivery during potassium depletion comes from micropuncture studies in which enhanced fractional fluid reabsorption in the proximal convoluted tubules has been reported (Capasso, Kinne, Malnic & Giebisch, 1986; Walter, Shore & Shirley, 1988).…”

Mechanisms of Distal–Nephron Li⁺ Reabsorption during Dietary K⁺ Restriction in Rats

“…Further evidence for competitive inhibition of Li + reabsorption by Na + in K-depleted rats comes from studies in which the tubular Na + concentration in the distal-nephron has been reduced by administration of a low-Na + diet in addition to a low-K + diet. These studies [4,15] have repeatedly demonstrated that FE Li is reduced to almost zero, indicating almost complete reabsorption of Li + by the amiloride-sensitive site when competition from tubular Na + is severely reduced.…”

“…Dietary K + restriction also leads to hyperpolarization of the apical membrane of the collecting ducts [14], and a decrease in the amount of Na + delivered to the amiloride-sensitive segment to K + -depleted rats has been demonstrated to increase distal tubular Li + reabsorption to almost 100% [4,15]. Apical membrane hyperpolarization of the cortical collecting ducts thus appears to be important in conditions associated with distal tubular Li + reabsorption, and the delivery of Na + to the amiloride-sensitive sites seems to be of utmost importance for the magnitude of distal tubular Li + reabsorption.…”

Alterations of Lithium Clearance in Rats by Different Modes of Lithium Administration

“…but it has also been demonstrated that the method cannot be used in rats and dogs given a low sodium diet because this leads to distal lithium reabsorption [4,11,18,[24][25][26]. W hether any reabsorption of lithium occurs in the distal ne phron when humans are maintained on a low sodium diet remains to be established [3,14).…”