| Abstract: | The renal actions of differing doses of sodium orthovanadate were studied in conscious and anesthetized female Wistar rats. In conscious rats, sodium orthovanadate was given by i.v. or i.p. injections or by mouth. The most pronounced renal effects were seen after a 5 mg/kg i.p. injection of sodium orthovanadate. Urine flow and sodium excretion increased approximately 400% and urine osmolality fell from 1108 to 549 mOsmol/kg . H2O. Higher doses of sodium orthovanadate (20, 30 and 50 mg/kg) injected i.p. did not cause diuresis and were toxic. In anesthetized rats undergoing a 0.9% NaCl diuresis, i.v. infusion of sodium orthovanadate at a dose of 5 mg/kg/hr significantly increased urine flow and the excretion of sodium, calcium, phosphorus, sulfur, magnesium and chlorine, whereas glomerular filtration rate was unaltered. In anesthetized rats undergoing a water diuresis, i.v. infusion of sodium orthovanadate (5 mg/kg/hr) markedly reduced free-water clearance, indicating that this compound inhibits tubular reabsorption of sodium and chloride in diluting nephron segments. Blood and renal tissue levels of vanadium, measured using emission spectrographic analysis, in rats infused with sodium orthovanadate were 4 times higher than the concentration of sodium orthovanadate (1--10 microM) needed to inhibit 50% of the Na-K-adenosine triphosphate activity of rat renal homogenates in vitro. These data suggest that sodium orthovanadate produces diuresis at least in part by inhibiting Na-K-adenosine triphosphatase and solute transport in the distal nephron, likely the ascending limb of the loop of Henle. |
