Time Course of Lithium‐induced Alterations in Renal and Endocrine Function in Normal and Brattleboro Rats With Hypothalamic Diabetes Insipidus

Abstract

I A lithium chloride (1.1 g/kg) supplemented diet was given to Long Evans (LE) and Brattleboro (DI) rats to investigate its actions in the presence (LE) and absence (DI) of vasopressin. 2 During the first 24 h, Li-supplemented LE rats displayed an initial water deficit (drinking less than renal output), increased plasma antidiuretic (ADH) titres and slightly increased plasma renin activities (PRA) and plasma osmolarities. Such changes were qualitatively similar to those seen in rats fed a normal diet, but deprived of water for 24 hours. After 12 days, the Li-supplemented rats had elevated plasma ADH titres, but reduced pituitary oxytocic and antidiuretic activities. 3 The urinary losses of Na, K and Cl exceeded dietary intakes in LE rats on the introduction of the Li-supplement, and the urinary osmolarity fell by 50%. Electrolyte balances were gradually reestablished, although drinking and urine production increased in parallel to reach twice the control values by day 12 of the supplement. 4 Aldosterone and corticosterone secretory rates and their peripheral plasma concentrations were unchanged both after 24 h and 28 days of the Li-supplement. 5 Li elicited no water deficit or saluresis in DI rats, and although the polyuria and polydipsia were exacerbated, urinary osmolarity did not change over the 12 day observation period. 6 Li increased Ca excretion in both rat types; after 12 days the PRA of DI but not LE animals was increased. 7 It is concluded that the overall renal actions of Li are tempered by vasopressin rather than adrenocorticosteroids.

Changes in cellular composition of kidney collecting duct cells in rats with lithium-induced NDI

“…It could be speculated that lithium can act as a mitogen. It may also be caused by an indirect effect of lithium treatment, e.g., due to the high vasopressin concentration that is known to be present in lithium-treated animals (2,4,15,38). Vasopressin has been shown to stimulate mesangial cell proliferation (14).…”