Influence of Renal Nerves and Sodium Balance on the Acute Antidiuretic Effect of Bendroflumethiazide in Rats with Diabetes Insipidus

• Published in: The Journal of pharmacology and experimental therapeutics 1997-09, Vol.282 (3), p.1155-1162
• Main Authors: Spannow, J, Thomsen, K, Petersen, J S, Haugan, K, Christensen, S
• Format: Article
• Language: English
• Subjects: Animals; Bendroflumethiazide - pharmacology; Diabetes Insipidus - drug therapy; Diabetes Insipidus - metabolism; Diuresis - drug effects; Diuretics; Glomerular Filtration Rate - drug effects; Kidney - innervation; Male; Rats; Rats, Brattleboro; Sodium - metabolism; Sodium Chloride Symporter Inhibitors - pharmacology
• ISSN: 0022-3565; 1521-0103

To examine the role of the renal nerves and sodium depletion for the acute antidiuretic response to bendroflumethiazide (BFTZ; 25 μg/hr) in rats with diabetes insipidus (DI), renal clearance experiments were performed in the following groups of conscious, chronically instrumented male Brattleboro rats with vasopressin-deficient DI: Control ( n = 7), BFTZ ( n = 9), BFTZ + sodium replacement ( n = 7) and BFTZ + chronic bilateral renal denervation ( n = 6). Urine flow rate and urinary sodium concentration were measured drop-by-drop with a sodium-sensitive electrode and by collection of urine in vials placed on an electronic balance. This allowed computer driven, servo-controlled, independent i.v. replacement of sodium and fluid losses, respectively. Mean arterial pressure, glomerular filtration rate (GFR) and proximal tubular water and sodium handling, assessed by lithium clearance (C Li ), were stable in the control group. BFTZ produced a marked antidiuretic response (ΔV = -79%; ΔUrine osmolality = +218%) associated with decreases in GFR (-28%), C Li (-62%), free water clearance (-100%) and plasma Na (-5 mM). Fractional water reabsorption was increased by 19% in the proximal tubules and by 7% in segments beyond. Sodium replacement did not modify the fall in GFR or the antidiuresis, but partly prevented the increase in fractional proximal water reabsorption. Bilateral renal denervation did not affect the response to BFTZ. We conclude that the acute antidiuretic effect of BFTZ is independent of sodium balance and renal nerve activity and is elicited by a reduction in GFR accompanied by an increase in fractional water reabsorption in the proximal tubules and in the distal nephron.