Role of sodium depletion in acute antidiuretic effect of bendroflumethiazide in rats with nephrogenic diabetes insipidus

The mechanisms underlying the acute antidiuretic response to bendroflumethi azide (BFTZ; 0.25 mg/h for 3 h) in rats with nephrogenic diabetes insipidus (NDI) was investigated. NDI was induced in conscious chronically instrumen ted 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 i nstrumented with permanent catheters. During experiments total body water c ontent was held constant by i.v. replacement of urine production (V) with 1 50 mM glucose. One group in addition received i.v. replacement of urinary s odium losses. In both models of NDI, BFTZ-induced antidiuresis was associat ed 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 decr ease 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 antidiures is in normal rats with water diuresis. It is concluded that in rats with ND I, thiazide-induced antidiuresis can be entirely explained by a fall in dis tal delivery of tubular fluid related to sodium depletion. This contrasts t he response in rats with central diabetes insipidus, where thiazides in add ition increase distal water reabsorption.