Lithium: ADH antagonism and ADH independent action in rats with diabetes insipidus

Treatment with lithium chloride (2 mmole/kg × 24 hr) caused a gradual increase in water intake, urine output, sodium and potassium excretion of rats; Na/K in the urine also increased. Lithium administration caused partial depletion of hypophyseal vasopressin and did not prevent the depletion caused by hypertonic stimulation. Sodium administration also caused partial depletion of hypophyseal vasopressin but had no significant effect on water intake or urine output. The inhibition of water intake and urine output by administration of ADH to rats with hereditary diabetes insipidus was antagonized by lithium chloride (2 mmole/kg); the dose of ADH necessary to cause 50% inhibition was increased by lithium more than 5-fold. Lithium did not inhibit in vitro kidney adenylate cyclase from rats with diabetes insipidus while it produced significant inhibition in kidney adenylate cyclase from control rats. Lithium injected into untreated rats with hereditary diabetes insipidus further increased their water intake, urine output and decreased their urine osmolality. Therefore, lithium also affected water balance through a mechanism unrelated to ADH. In rats with D.I., lithium did not increase sodium excretion but decreased potassium excretion, thus Na/K in the urine was increased. The possible interaction of lithium with ADH and with aldosterone is discussed.