Renal tubular effects of sodium fluoride

Administration of sodium fluoride results in vasopressin-resistant polyuric "renal failure" resembling nephrogenic diabetes insipidus. However, the renal tubular site of action of fluoride is not clear. Fischer 344 rats received acute i.v. infusions of sodium fluoride (0.3, 1.47 and 2.20 mumol/min/kg b.wt.) for 2.5 hr which resulted in dissipation of the renal medullary tissue osmotic gradient and a sustained, dose-related increase in fractional sodium excretion and urine flow. In additional experiments, free water reabsorption and excretion were decreased by fluoride, but the decrease in free water excretion occurred only when the fluoride-induced polyuria preceded the onset of the water diuresis. Slices of renal medulla from fluoride-treated rats had lower cyclic AMP concentrations than did slices from control rats and the responsiveness of the medullary tissue to vasopressin was markedly reduced. These data indicate that the fluoride ion dissipates the concentration gradient in the renal medulla largely by inhibiting NaCl reabsorption in the ascending limb of Henle's loop and inhibits antidiuretic hormone-mediated water reabsorption across the collecting duct.