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THE EFFECT OF CHLORPROPAMIDE ON WATER BALANCE IN PITRESSIN‐TREATED BRATTLEBORO RATS

1 The daily administration of a 5% glucose solution to the heterozygous Brattleboro rat produced an experimental model in a comparable state of polydipsia and polyuria to the homozygous rat with diabetes insipidus (DI). 2 The effect of chlorpropamide on water metabolism was then examined in both the homozygous DI rat treated with sub maximal doses of pitressin tannate in oil (Pitressin), and in the glucose‐hydrated heterozygous rat with and without simultaneous pitressin therapy. 3 A dose‐response curve for chlorpropamide (5, 10, and 20 mg/24 h) in DI rats treated with Pitressin (25 mu/24 h) indicated that the drug decreased fluid intake further, but only by a maximum of 13.8% (at the 20 mg/24 h dose of chlorpropamide), differing markedly from results obtained in patients with diabetes insipidus. A second experiment in which chlorpropamide (5 mg/24 h) was administered to DI rats treated with Pitressin (either 25 or 50 mu/24 h) confirmed the lack of any significant drug‐effect on water metabolism in these animals. 4 Chlorpropamide (20 mg/24 h), when administered alone or simultaneously with a submaximal dose of Pitressin (25 mu/24 h), had no obvious effect on the fluid intake of glucose‐hydrated heterozygous rats. The absence of any action by chlorpropamide on water metabolism was confirmed in these experimental animals using 5 mg/24 h of the drug together with Pitressin (either 25 or 50 mu/24 hours). 5 Indirect evidence for the slower growth‐rate in the DI rat being due to an insufficient daily calorific intake was obtained from the study on glucose‐hydrated heterozygous rats.