Abstract
Can loop diuretics like ethacrynic acid and furosemide, when administered intravenously, significantly alter ion transport and fluid dynamics in CNS? To shed light on this unresolved issue, we tested the ability of these agents to effect redistribution of Na, K and Cl in adult rat brain. Cl penetration into various CNS regions was assessed as the volume of distribution, i.e., uptake, of36Cl from blood. Ethacrynic acid and furosemide (50 mg/kg IV) reduced by 20–30% the rate of permeation of36Cl across the blood-CSF barrier, and they elevated [K] and [Cl] in choroid plexus (CP) by 15–25%. The loop diuretic-induced buildup of K and Cl in CP (lateral and 4th ventricle) was likely a reflection of decreased movement of these ions across the apical membrane into CSF.36Cl activity in parietal cortex and pons-medulla decreased in treatment with furosemide and ethacrynic acid, due to slowing of Cl transport across blood-brain and/or blood-CSF barriers. Our inhibitory findings in intact rats are consistent with those from previous in vitro experiments demonstrating diminution by loop diuretics of Na, K and Cl transport across isolated CP membranes.
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Johanson, C. E., Sweeney, S. M., Parmelee, J. T., and Epstein, M. H. 1990. Cotransport of sodium and chloride by the adult mammalian choroid plexus. Am. J. Physiol. 258:C211-C216.
Bairamian, D., Johanson, C. E., Parmelee, J. T., and Epstein, M. H. 1991. Potassium cotransport with sodium and chloride in the choroid plexus. J. Neurochem. 56:1623–1629.
Johanson, C. E., and Murphy, V. A. 1990. Acetazolamide and insulin alter choroid plexus epithelial cell [Na+], pH and volume. Am. J. Physiol. 258:F1538-F1546.
Javaheri, S., Freidel, J. F., and Davis, P. J. 1989. Furosemide and cerebrospinal fluid ions during acute respiratory acidosis. J. Appl. Physiol. 67:563–569.
Murphy, V. A., and Johanson, C. E. 1989. Acidosis, acetazolamide, and amiloride: Effects on22Na transfer across the blood-brain and blood-CSF barriers. J. Neurochem. 52:1058–1063.
Javaheri, S. 1991. Role of NaCl cotransport in cerebrospinal fluid production: effects of loop diuretics. J. Appl. Physiol. 71:795–800.
Domer, F. 1969. Effects of diuretics on cerebrospinal fluid formation and potassium movement. Exper. Neurol. 24:54–64.
Reed, D. J. 1969. The effect of furosemide on cerebrospinal fluid flow in rabbits. Arch. Int. Pharmacodyn. Ther. 178:324–330.
Miner, L. C., and Reed, D. J. 1971. The effect of ethacrynic acid on sodium uptake into the cerebrospinal fluid of the rat. Arch. Int. Pharmacodyn. 190:316–321.
McCarthy, K. D., and Reed, D. J. 1974. The effect of acetazolamide and furosemide on cerebrospinal fluid production and choroid plexus carbonic anhydrase activity. J. Pharmacol. Exp. Ther. 189:194–201.
Vogh, B. P., and Langham, Jr. M. R. 1981 The effect of furosemide and bumetanide on cerebrospinal fluid formation. Brain Res. 221:171–183.
Melby, J. M., Miner, L. C., and Reed, D. J. 1982. Effect of acetazolamide and furosemide on the production and composition of cerebrospinal fluid from the choroid plexus. Can. J. Physiol. Pharmacol. 60:405–409.
Miller, T. B., Wilkinson, H. A., Rosenfield, S. A., and Furuta, T. 1986. Intracranial hypertension and cerebrospinal fluid production in dogs: Effects of furosemide. Exper. Neurol. 94:66–80.
Johnson, D. C., Singer, S., Hoop, B., and Kazemi, H. 1987. Chloride flux from blood to CSF: inhibition by furosemide and bumetanide. J. Appl. Physiol. 63:1591–1600.
Smith, Q. R., and Johanson, C. E. 1991. Chloride efflux from isolated choroid plexus. Brain Res., 562:306–310, 1991.
Palfrey, H. C., and Rao, M. C., 1983. Na/K/Cl co-transport and its regulation. J. Exp. Biol. 106:43–54.
Buhrley, L. E., and Reed, D. J. 1972. The effect of furosemide on sodium-22 uptake into cerebrospinal fluid and brain. Exp. Brain Res. 14:503–510.
Lorenzo, A. V., Greene, C. S., Hornig, G. W., Zavala, M., and Welch, K. 1989. The effect of furosemide on intracranial pressure and hemorrhage in preterm rabbits. J. Neurosurg. 70:785–792.
Knuckey, N. W., Fowler, A. G., Johanson, C. E., Nashold, J. R. B., and Epstein, M. H. 1991. Cisterna magna microdialysis of22Na to evaluate ion transport and cerebrospinal fluid dynamics. J. Neurosurgery 74:965–971.
Smith, Q. R., Woodbury, D. M., and Johanson, C. E. 1982. Kinetic analysis of Cl-36, Na-22 and H-3 mannitol uptake into the in vivo choroid plexus-cerebrospinal fluid system: Ontogeny of the blood-brain and blood-CSF barriers. Dev. Brain Res. 3:181–198.
Harbut, R., and Johanson, C. E. 1986. Third ventricle choroid plexus function and its response to acute perturbations in plasma chemistry. Brain Res. 374:137–146.
Murphy, V. A., and Johanson, C. E. 1990. Na+-H+ exchange in choroid plexus and CSF in acute metabolic acidosis or alkalosis. Am. J. Physiol. 258:F1528-F1537.
Smith, Q. R., and Johanson, C. E., 1980. Effect of carbonic anhydrase inhibitors and acidosis on choroid plexus epithelial cell sodium and potassium. J. Pharmacol. and Exper. Ther. 215:673–680.
Preston, J. E., Johanson, C. E., and Parmelee, J. T. 1990. Chloride efflux from the choroid plexus of infant and adult rats. Soc. for Neurosci. Abs. 16:45.
Betz, A. L. 1983. Sodium transport from blood to brain: Inhibition by furosemide and amiloride. J. Neurochem. 41:1158–1164.
Betz, A. L. 1986. Transport of ions across the blood-brain barrier. Fed. Proceed. 45:2050–2054.
Johanson, C. E., Murphy, V. A., Bairamian, D., and Epstein, M. H. 1989. Exchange vs. cotransport of Na and Cl across the barriers interfacing cerebrospinal fluid and brain with blood. Pages 303–311in Hoff, J. and Betz, A. (eds.), Intracranial Pressure VII, Springer-Verlag, New York.
Weiss, M. H., and Wertman, N. 1978. Modulation of CSF production by alteration in cerebral perfusion pressure. Arch. Neurol. 35:727–729.
Murphy, V. A., and Johanson, C. E. 1985. Adrenergic-induced enhancement of brain barrier system permeability to small nonelectrolytes: Choroid plexus versus cerebral capillaries. J. Cereb. Blood Flow. Metab. 5:401–412.
Zeuthen, T. 1991. Secondary active transport of water across ventricular cell membrane of choroid plexus epithelium of necturus maculosus. J. Physiol. 444:153–173.
Saito, Y., and Wright, E. M. 1983. Bicarbonate transport across the frog choroid plexus and its control by cyclic nucleotides. J. Physiol. 336:635–648.
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Johanson, C.E., Murphy, V.A. & Dyas, M. Ethacrynic acid and furosemide alter Cl, K, and Na distribution between blood, choroid plexus, CSF, and brain. Neurochem Res 17, 1079–1085 (1992). https://doi.org/10.1007/BF00967284
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DOI: https://doi.org/10.1007/BF00967284