Abstract
The hypothesis that in conditions of hyperbaric oxygenation, nitric oxide (NO) modulates the vasodilatory effect of CO2 in the brain and thus accelerates the neurotoxic action of oxygen was verified experimentally. Conscious rats breathed atmospheric air or oxygen at 5 atm and blood flow in the striatum was measured before and after inhibition of carbonic anhydrase with acetazolamide, which causes retention of CO2 in the brain. Acetazolamide (35 mg/kg) increased blood flow in the animals when breathing air by 38 ± 7.4% (p < 0.01), while preliminary inhibition of NO synthase with Nω-nitro-L-arginine-methyl ester (L-NAME, 30 mg/kg) significantly weakened its vasodilatory action. Inhibition of carbonic anhydrase in animals breathing hyperbaric oxygen at 5 atm prevented cerebral vasoconstriction, increased brain blood flow, and accelerated the development of oxygen convulsions. The vasodilatory effect of acetazolamide in hyperbaric oxygenation was significantly reduced in animals pretreated with the NO synthase inhibitor, such that the latent period of convulsions increased. The results obtained here provide evidence that in conditions of extreme hyperoxia, NO modulates the cerebral hyperemia developing in conditions of CO2 retention in the brain and accelerates the development of the neurotoxic actions of hyperbaric oxygen.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
D. R. Gutsaeva, A. N. Moskvin, V. B. Kostkin, and I. T. Demchenko, “The role of nitric oxide in the postnatal resistance of rats to the neurotoxic effects of hyperbaric oxygen,” Zh. Evolyuts. Biokhim. Fiziol., 38, No.2, 189–190 (2002).
I. T. Demchenko, A. E. Boso, S. Yu. Zhilyaev, A. N. Moskvin, D. R. Gutsaeva, D. N. Atochin, P. B. Bennet, and K. A. Piantadosi, “The role of nitric oxide in cerebral vasoconstriction in rats breathing oxygen under pressure,” Ros. Fiziol. Zh. im. I. M. Sechenova, 86, No.12, 1594–1603 (2000).
S. Yu. Zhilyaev, A. N. Moskvin, D. R. Gutsaeva, I. V. Churilina, and I. T. Demchenko, “Hyperbaric vasoconstriction in the brain is mediated by inactivation of nitric oxide by superoxide anions,” Ros. Fiziol. Zh. im. I. M. Sechenova, 88, No.5, 553–559 (2002).
A. G. Zhironkin, Oxygen. Physiological and Toxic Actions [in Russian], Nauka, Leningrad (1972).
G. L. Zal’tsman, B. N. Ponomarev, and A. I. Selivra, “The bioelectrical activity of various brain centers during the formation of oxygen epilepsy in dogs,” in: Hyperbaric Epilepsy and Anesthesia [in Russian], Nauka, Leningrad (1968).
A. N. Moskvin, S. Yu. Zhilyaev, O. I. Sharapov, T. F. Platonova, D. R. Gutsaeva, V. B. Kostkin, and I. T. Demchenko, “Brain blood flow modulates the neurotoxic action of hyperbaric oxygen via neuronal and endothelial nitric oxide,” Ros. Fiziol. Zh. im. I. M. Sechenova, 88, No.7, 873–880 (2002).
A. I. Selivra, Hyperbaric Oxygenation [in Russian], Nauka, Leningrad (1983).
J. D. Balantine, Pathology of Oxygen Toxicity, Academic Press, New York (1982).
J. W. Bean, J. Lignell, and J. Coulson, “Regional cerebral blood flow, O2, and EEG in exposure to O2 at high pressure,” J. Appl. Physiol., 31, 235–324 (1971).
I. T. Demchenko, A. E. Bosso, A. R. Whorton, and C. A. Piantadosi, “Nitric oxide production is enhanced in rat brain before oxygen-induced convulsions,” Brain Res., 917, 253–261 (2001).
D. L. Ehrenreich, R. A. Burns, R. W. Alman, and J. F. Fazekas, “Influence of acetazolamide on cerebral blood flow,” Arch. Neurol., 5, 227–231 (1961).
F. Gotoh, J. S. Meyer, and M. Tomita, “Carbonic anhydrase inhibition and cerebral venous blood gases and ions in man,” Arch. Intern. Med., 117, 39–43 (1966).
F. M. Faraci and D. D. Heistad, “Regulation of the cerebral circulation: role of endothelium and potassium channels,” Physiol. Rev., 78, 53–97 (1998).
D. Heuser, J. Astrup, N. A. Lassen, and B. Betz, “Brain carbonic acid acidosis after acetazolamide,” Acta Physiol. Scand., 93, 385–390 (1975).
C. Iadecola and F. Zhang, “Nitric oxide dependent and independent components of cerebrovasodilation elicited by hypercapnia,” Amer. J. Physiol., 266, R546–R552 (1994).
C. Iadecola, D. D. Pellegrino, M. A. Moskowitz, and N. Lassen, “Nitric oxide synthesis inhibition and cerebrovascular regulation,” J. Cereb. Blood Flow Metab., 14, 175–192 (1994).
B. Kiss, S. Dallinger, O. Findi, G. Rainer, H. G. Eichler, and L. Schmetter, “Acetazolamide-induced cerebral and ocular vasodilation in humans is independent of nitric oxide,” Amer. J. Physiol., 276, R1661–R1667 (1999).
C. J. Lambertsen, R. E. Krough, D. Y. Cooper, et al., “Oxygen toxicity. Effects in man of oxygen inhalation at 1 and 3.5 atmospheres upon blood gas transport, cerebral circulation and cerebral metabolism,” J. Appl. Physiol., 1953, No.5, 471–486 (1999).
U. Lindauer, J. Vogt, S. Schuh-Hofer, J. P. Dreier, and U. Dirnagl, “Cerebrovascular vasodilation to extraluminal acidosis occurs via combined activation of ATP-sensitive and Ca2+-activated potassium channels,” J. Cereb. Blood Flow. Metab., 23, 1227–1238 (2003).
S. Moncada, R. M. J. Palmer, and E. A. Higgs, “Nitric oxide. Physiology, pathophysiology and pharmacology,” Pharmacol. Rev., 43, 109–142 (1991).
L. J. Pellegrino, A. C. Pellegrino, and A. J. Cushman, A Stereotaxic Atlas of the Rat Brain, Plenum Press (1979).
D. Torbati, D. Parolla, and S. Lavy, “Blood flow in rat brain during exposure to high oxygen pressure,” Aviat. Space Environ. Med., 49, 963–967 (1978).
J. Tuttenberg, A. Heimann, and O. Kempski, “Nitric oxide modulates cerebral blood flow stimulation by acetazolamide in the rat cortex: a laser Doppler scanning study,” Neurosci. Lett., 315, 65–68 (2001).
C. D. Wood, “Acetazolamide and CO2 in hyperbaric oxygen toxicity,” Undersea Biomed. Res., 9, No.1, 15–21 (1982).
Author information
Authors and Affiliations
Additional information
__________
Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 90, No. 4, pp. 428–436, April, 2004.
Rights and permissions
About this article
Cite this article
Gutsaeva, D.R., Moskvin, A.N., Zhilyaev, S.Y. et al. The Roles of Nitric Oxide and Carbon Dioxide Gas in the Neurotoxic Actions of Oxygen under Pressure. Neurosci Behav Physiol 35, 751–756 (2005). https://doi.org/10.1007/s11055-005-0119-9
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/s11055-005-0119-9