The effect of furosemide on sodium-22 uptake into cerebrospinal fluid and brain

Movement of sodium from plasma into the cerebrospinal fluid (CSF) in against an electrochemical gradient and this process is probably dependent upon active sodium transport. CSF production is inhibited by chemical agents known to interfere with active transport of sodium in the kidney and other systems. Since there are many similarities between renal tubule and choroid plexus epithelial cells, in was of interest to ascertain the effect of a potent saluretic agent on the uptake of radioactive sodium in the CSF and brain. The effect of furosemide on the uptake of sodium-22 into the CSF and cerebral cortex of nephrectomized rats was studies. Furosemide is a potent saluretic agent which abolishes the renal medullary sodium gradient and decreases the short-circuit current in the frog skin and toad bladder. Furosemide, 1 mg/kg, was injected into the left lateral ventricle of the brain, sodium-22 was injected intraperitoneally and the uptake of the isotope into CSF, cerebral cortex, skeletal muscle, and brain was measured at intervals of 0.25 hour after the sodium-22 was administered. During the initial 4 hour period after injection of the sodium-22, the uptake of the isotope was decreased in the furosemide-treated animals. The maximum reduction in uptake occurred at the .0.25-hour time period. The CSSF radioactivity in the treated animals, measured as sodium relative specific activity (RSA), was 37% less than that of the control animals. At 24 hours, there was no difference to sodium-22 uptake in the CSF between the control and treated animals. The uptake of sodium-22 into cerebral cortex was decreased in the treated animals. The largest reduction in activity, 18%, occurred 2 hours after the injection of the isotope. Since the brain extracellular space and the CSF appear to be in relatively free communication, this reduction could be the indirect result of the decreased uptake of sodium-22 into the CSF. Furosemide has slight carbonic anhydrase inhibiting activity but it is probably inadequate to explain fully the reduced uptake of radioactive sodium into the CSF. It is suggested that the decrease in sodium-22 uptake into CSF and brain in the furosemide-treated animals may be caused by inhibition of active sodium transport in the choroid plexus.