Potentiation of the Antidiuretic Effect of Vasopressin by Chlorpropamide

Abstract

Several groups of workers have established that chlorpropamide, an oral hypoglycemic agent, reduces urine flow in some individuals with diabetes insipidus (DI). The present study was designed to examine the effectiveness of this agent in rats with total hypothalamic diabetes insipidus (Brattleboro strain). In the first type of experiment chlorpropamide was administered ip to DI rats after appropriate control urine collections. No effect was found on urine volume, osmolality, sodium concentration, or potassium concentration. In the second group of experiments the DI rats were pretreated with chlorpropamide 2 hr before the administration of a minimally effective dose of arginine-vasopressin. In these experiments the urine osmolality was increased, urine volume decreased, and both sodium and potassium concentrations of the urine were increased significantly compared to control animals not given chlorpropamide. In the next set of experiments similar results were found with chronically administered chlorpropamide. Finally, the effect of vasopressin tannate in oil, administered in subthreshold doses, was also enhanced by oral chlorpropamide. It appears, therefore, that chlorpropamide potentiates vasopressin in diabetes insipidus, but has no direct antidiuretic effect of its own. (Endocrinology86: 1028, 1970)