Advertisement

Carbonic Anhydrase Inhibition and Cerebral Cortical Oxygenation in the Rat

  • Joseph C. LaManna
  • Kimberly A. McCracken
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 277)

Abstract

The carbonic anhydrase inhibitor, acetazolamide (Maren, 1967), has been used clinically for many years as a treatment for the prevention of the symptoms, primarily headaches, of acute exposure to altitude hypoxia, as originally demonstrated by Cain and Dunn (1966). This effect was thought to be due to a drug-induced metabolic acidosis that compensated for an altitude-induced respiratory alkalosis. Furthermore, it had already been noticed that acetazolamide administration was followed by increased cerebral blood flow (Cotev et al., 1968; Ehrenreich et al., 1961; Posner and Plum, 1960), an observation that has often been confirmed since. Nevertheless, the effects of acetazolamide on metabolism and blood flow in the brain and their relationships to the physiological mechanisms of action of acetazolamide have not been well studied.

Keywords

Cerebral Blood Flow Carbonic Anhydrase Regional Cerebral Blood Flow Blood Flow Rate Acute Mountain Sickness 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Cain, S.M., and Dunn, J.E., 1966, Low doses of acetazolamide to aid accommodation of men to altitude, J. Appl. Physiol., 21: 1195–1200.PubMedGoogle Scholar
  2. Cotev, S., Lee, J., and Severinghaus, J.W., 1968, The effects of acetazolamide on cerebral blood flow and cerebral tissue P02, Anesthesiol., 29: 471–477.CrossRefGoogle Scholar
  3. Ehrenreich, D.L., Burns, R.A., Alman, R.W., and Fazekas, J.F., 1961, Influence of acetazolamide on cerebral blood flow, Arch. Neurol., 5: 125–130.CrossRefGoogle Scholar
  4. Forwand, S.A., Landowne, M., Follansbee, J.N., and Hansen, J.E., 1968, Effect of acetazolamide on acute mountain sickness, New Engl. J. Med., 279: 839–845.PubMedCrossRefGoogle Scholar
  5. Giacobini, E., 1962, A cytochemical study of the localization of carbonic anhydrase in the nervous system, J. Neurochem., 9: 169–177.PubMedCrossRefGoogle Scholar
  6. Gotoh, F., and Shinohara, Y., 1977, Role of carbonic anhydrase in chemical control and autoregulation of cerebral circulation, Int. J. Neurol., 11: 219–227.PubMedGoogle Scholar
  7. Grieb, P., and Forster, R.E., 1981, The effect of acetazolamide on brain O2 metabolism, in: “Oxygen Transport to Tissue (Adv. Physiol. Sci., vol 25),” A.G.B. Kovach, E. Dora, M. Kessler, and I.A. Silver, eds., pp. 271–272, Akademiai Kiado, Budapest.Google Scholar
  8. Harik, S.I., and LaManna, J.C., 1988, Vascular perfusion and blood-brain glucose transport in acute and chronic hyperglycemia, J. Neurochem., 51: 1924–1929.PubMedCrossRefGoogle Scholar
  9. Harvey, T.C., Raichle, M.E., Winterhorn, M.H., Jensen, J., Lassen, N.A., Richardson, N.V., and Bradwell, A.R., 1988, Effect of carbon dioxide in acute mountain sickness: a rediscovery, Lancet, ii: 639–641.CrossRefGoogle Scholar
  10. Hauge, A., Nicolaysen, G., and Thoresen, M., 1983, Acute effects of acetazolamide on cerebral blood flow in man, Acta Physiol. Scand., 117: 233–239.PubMedCrossRefGoogle Scholar
  11. Heuser, D., Astrup, J., Lassen, N.A., and Betz, E., 1975, Brain carbonic acid acidosis after acetazolamide, Acta Physiol. Scand., 93: 385–390.PubMedCrossRefGoogle Scholar
  12. Johanson, C.E., 1984, Differential effects of acetazolamide, benzolamide and systemic acidosis on hydrogen and bicarbonate gradients across the apical and basolateral membranes of the choroid plexus, J. Pharmacol. Exp. Ther., 231: 502–511.PubMedGoogle Scholar
  13. Kjällquist, A., Nardini, M., and Siesjö, B.K., 1969, The effect of acetazolamide upon tissue concentrations of bicarbonate, lactate, and pyruvate in the rat brain, Acta Physiol. Scand., 77: 241–251.PubMedCrossRefGoogle Scholar
  14. Kreisman, N.R., Sick, T.J., LaManna, J.C., and Rosenthal, M., 1981, Local tissue oxygen tension — cytochrome a,a3 redox relationships in rat cerebral cortex in vivo, Br. Res., 218: 161–174.Google Scholar
  15. LaManna, J.C., Light, A.I., Peretsman, S.J., and Rosenthal, M., 1984, Oxygen insufficiency during hypoxic hypoxia in rat brain cortex, Br. Res., 293: 313–318.CrossRefGoogle Scholar
  16. LaManna, J.C., Sick, T.J., Pikarsky, S.M., and Rosenthal, M., 1987, Detection of an oxidizable fraction of cytochrome oxidase in intact rat brain, Am. J. Physiol., 253: C477–C483.PubMedGoogle Scholar
  17. LaManna, J.C., McCracken, K.A., and Strohl, K.P., 1989, Changes in regional cerebral blood flow and sucrose space after 3–4 weeks of hypobaric hypoxia (0.5 ATM), in: “Oxygen Transport to Tissue XI (Advances in Experimental Medicine and Biology, v. 247),” K. Rakusan, G.P. Biro, T.K. Goldstick, and Z. Turek, eds., pp. 471–477, Plenum Publishing Corp, New York.CrossRefGoogle Scholar
  18. Laux, B.E., and Raichle, M.E., 1978, The effect of acetazolamide on cerebral blood flow and oxygen utilization in the rhesus monkey, J. Clin. Invest., 62: 585–592.PubMedCrossRefGoogle Scholar
  19. Lockwood, A.H., LaManna, J.C., Snyder, S., and Rosenthal, M., 1984, Effects of acetazolamide and electrical stimulation on cerebral oxidative metabolism as indicated by the cytochrome oxidase redox state, Br. Res., 308: 9–14.CrossRefGoogle Scholar
  20. Lund-Andersen, H., 1979, Transport of glucose from blood to brain, Physiol. Rev., 59: 305–352.PubMedGoogle Scholar
  21. Maren, T.H., 1967, Carbonic anhydrase: chemistry, physiology, and inhibition, Physiol. Rev., 47: 595–781.PubMedGoogle Scholar
  22. Meyer, J.S., Gotoh, F., and Tazaki, Y., 1961, Inhibitory action of carbon dioxide and acetazolamide in seizure activity, Electroenceph. clin. Neurophysiol., 13: 762–775.CrossRefGoogle Scholar
  23. Mithoefer, J.C., 1959, Inhibition of carbonic anhydrase: Its effect on carbon dioxide elimination by the lungs, J. Appl. Physiol., 14: 109–115.PubMedGoogle Scholar
  24. Posner, J.B., and Plum, F., 1960, The toxic effects of carbon dioxide and acetazolamide in hepatic encephalopathy, J. Clin. Invest., 39: 1246–1258.PubMedCrossRefGoogle Scholar
  25. Sage, J.I., Van Uitert, R.L., and Duffy, T.E., 1981, Simultaneous measurement of cerebral blood flow and unidirectional movement of substances across the blood-brain barrier: theory, method, and application to leucine, J. Neurochem., 36: 1731–1738.PubMedCrossRefGoogle Scholar
  26. Vorstrup, S., Henriksen, L., and Paulson, O.B., 1984, Effect of acetazolamide on cerebral blood flow and cerebral metabolic rate for oxygen, J. Clin. Invest., 74: 1634–1639.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Joseph C. LaManna
    • 1
  • Kimberly A. McCracken
    • 1
  1. 1.Departments of Neurology and Physiology/BiophysicsCase Western Reserve University School of Medicine and University HospitalsClevelandUSA

Personalised recommendations