Potentiation of Vasopressin Action by Chlorpropamide<i>in Vivo</i>

Abstract

Studies were performed to determine the mechanism of the antidiuretic activity of chlorpropamide. When the drug was given to Brattleboro rats homozygous for hereditary hypothalamic diabetes insipidus (DI) no antidiuretic effect was found. The absence of an antidiuretic effect was also found in normal rats and rats heterozygous for DI. However, when rats homozygous for DI were pretreated with chlorpropamide, the antidiuretic effect of small doses of vasopressin was found to be significantly enhanced when compared to the effect of vasopressin injected into rats not pretreated with chlorpropamide. The data suggest that a mechanism of chloropropamide action in DI is by means of potentiation of the effect of small amounts of endogenous vasopressin acting on the renal tubule. In the presence of large amounts of vasopressin the potentiating action of chlorpropamide is no longer distinguishable from the effects of vasopressin alone. The drug does not appear to have a direct effect on the renal concentrating mecha...