Role of sodium depletion in acute antidiuretic effect of bendroflumethiazide in rats with nephrogenic diabetes insipidus.
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.
Janjua
N R
NR
Department of Pharmacology, The Panum Institute, University of Copenhagen, Denmark.
Jonassen
T E
TE
Langhoff
S
S
Thomsen
K
K
Christensen
S
S
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001539:Bendroflumethiazide / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D018500:Diabetes Insipidus, Nephrogenic / Q000139:chemically induced / Q000378:metabolism*; D004231:Diuresis / Q000187:drug effects*; D004232:Diuretics; D005260:Female; D007262:Infusions, Intravenous; D008094:Lithium; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000502:physiology* / Q000652:urine; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology*
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; C076251:mozavaptan; D001539:Bendroflumethiazide; D008094:Lithium; D012964:Sodium