Effect of antidiuretic drugs in rats with lithium-induced polyuria.

Abstract

Abstract The effect of various antidiuretic drugs was studied in rats with lithium‐induced polyuria. Constant polyuria (urine volume > 150 ml/24 hrs, Uosm < 200 mosmol/kg) was induced in male Wistar rats by administration of LiCl in the food for 2–3 months before the experiments. Body weight, food consumption and urine volume and osmolality were recorded daily. After a 7 days control period, drugs were administered once or twice daily for 7 days. Bendroflumethiazide, 0.4, 2 and 10 mg/kg daily orally, produced a reversible, dose‐dependent antidiuretic response as indicated by a decrease in free water clearance. After 10 mg/kg, negative free water clearance was induced and the urine flow was reduced to one third. Diazoxide, chlorpropamide and carbamazepine did not significantly affect urine volume or osmolality at dose levels producing no effects on food consumption or body weight. The antidiuretic response to a thiazide diuretic and the lack of response to drugs known to have antidiuretic action in pituitary diabetes insipidus, lend support for the nephrogenic basis of the concentration defect induced by lithium.