Chronic lithium treatment inhibits amiloride-sensitive sodium transport in the rat distal nephron

Chronic treatment of rats with lithium leads to Nai loss and a reduced antinatriuretic response to aldosterone, suggesting that lithium reduces conductive Na+ transport in the distal nephron. This was investigated in the present study by measuring the renal response to aldosterone infusion followed by amiloride in chronically instrumented conscious rats given lithium for 3 to 4 weeks to achieve plasma Li+ concentrations of approximately 0.5 mM. A servo-controlled infusion system was used to maintain sodium and water homeostasis, thereby preventing misinterpretation of the findings as a consequence of drug-induced changes in Nai balance. In a control group of rats, Na+ excretion decreased in response to aldosterone (p <.01) and subsequent amiloride administration led to a marked increase in Na+ excretion (p <.001). In contrast, in the lithium-treated group, there was no significant response to either aldosterone or amiloride. It is concluded that long-term treatment with lithium, even when plasma Li+ concentrations are below 1 mM, reduces aldosterone-stimulated Na+ transport through the amiloride-sensitive Na+ channels in the principal cells of the distal nephron.