The mechanisms underlying the acute antidiuretic response to
bendroflumethiazide (BFTZ; 0.25 mg/h for 3 h) in rats with
nephrogenic diabetes insipidus (NDI) was investigated. NDI was induced in conscious chronically instrumented female Wistar rats either by chronic
lithium administration (40-60 mmol Li/kg of diet for 4 weeks) or by acute infusion of V2 antagonist
OPC-31260 (0.2 mg/h). Renal clearance experiments were performed in conscious rats instrumented with permanent
catheters. During experiments total body water content was held constant by i.v. replacement of urine production (V) with 150 mM
glucose. One group in addition received i.v. replacement of urinary
sodium losses. In both models of NDI, BFTZ-induced antidiuresis was associated with a decrease in the delivery of tubular fluid to the distal nephron, as measured by
lithium clearance (C(Li)). Both the antidiuresis and the decrease in C(Li) could be prevented by
sodium replacement. BFTZ did not affect distal water handling as measured by V/C(Li). BFTZ did not induce antidiuresis in normal rats with water diuresis. It is concluded that in rats with NDI,
thiazide-induced antidiuresis can be entirely explained by a fall in distal delivery of tubular fluid related to
sodium depletion. This contrasts the response in rats with
central diabetes insipidus, where
thiazides in addition increase distal water reabsorption.