The Effect of Chlorpropamide on Water Balance in Pitressin‐treated Brattleboro Rats

Abstract

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 submaximal 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). SIndirect 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.

Vasopressin induces apical expression of caveolin in rat kidney collecting duct principal cells

“…Experiments on AQP2 localization and urine concentration were performed to confirm that the BB rats used in our experiments indeed responded appropriately to DDAVP treatment (27,55). As expected, DDAVP induced a sustained, time-dependent increase in urine osmolality in BB rats (Fig.…”

Calcitonin Has a Vasopressin-like Effect on Aquaporin-2 Trafficking and Urinary Concentration

“…Previous studies showed that a reduction of urinary output is also correlated with reduced water intake in VPtreated Brattleboro rats. 48,49 Furthermore, although acute treatment of Brattleboro rats with physiologic doses of VP had no reported effect on GFR, 50,51 direct measurements of GFR were not performed in these studies, and a contribution of a change in GFR to the observed effect of CT cannot be ruled out.…”

A novel therapeutic effect of statins on nephrogenic diabetes insipidus

“…Brattleboro rats lacking AVP because of spontaneous mutation of the AVP gene , were treated with intraperitoneal administration of simvastatin to a final plasma concentration of 200 μM, without any visible side effect . Simvastatin caused a decrease in urinary volume associated with consistently increased urine osmolality.…”