Neuroscience and Behavioral Physiology

, Volume 33, Issue 8, pp 783–787 | Cite as

Hyperoxic Vasoconstriction in the Brain Is Mediated by Inactivation of Nitric Oxide by Superoxide Anions

  • S. Yu. Zhilyaev
  • A. N. Moskvin
  • T. F. Platonova
  • D. R. Gutsaeva
  • I. V. Churilina
  • I. T. Demchenko


The hypothesis that decreases in brain blood flow during respiration of hyperbaric oxygen result from inactivation of nitric oxide (NO) by superoxide anions (O2) is proposed. Changes in brain blood flow were assessed in conscious rats during respiration of atmospheric air or oxygen at a pressure of 4 atm after dismutation of O2 with superoxide dismutase or suppression of NO synthesis with the NO synthase inhibitor L-NAME. I.v. administration of superoxide dismutase increased brain blood flow in rats breathing air but was ineffective after previous inhibition of NO synthase. Hyperbaric oxygenation at 4 atm induced decreases in brain blood flow, though prior superoxide dismutase prevented hyperoxic vasoconstriction and increased brain blood flow in rats breathing hyperbaric oxygen. The vasodilatory effect of superoxide dismutase in hyperbaric oxygenation was not seen in animals given prior doses of the NO synthase inhibitor. These results provide evidence that one mechanism for hyperoxic vasoconstriction in the brain consists of inactivation of NO by superoxide anions, decreasing its basal vasorelaxing action.

nitric oxide superoxide anion brain blood flow hyperbaric oxygenation superoxide dismutase 


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  1. 1.
    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).Google Scholar
  2. 2.
    A. G. Zhironkin, Oxygen. Physiological and Toxic Actions [in Russian], Nauka, Leningrad (1972).Google Scholar
  3. 3.
    Yu. S. Zagvazdin, S. Yu. Zhilyaev, Yu. N. Morgalev, and D. N. Atochin, “Quantitative evaluation of local brain blood flow by clearance using inhalation and electrochemical detection of hydrogen, ” Fiziol. Zh. SSSR, 72, No. 12, 1693–1696 (1986).Google Scholar
  4. 4.
    A. I. Selivra, Hyperbaric Oxygenation [in Russian], Nauka, Leningrad (1983).Google Scholar
  5. 5.
    J. S. Beckman and W. H. Koppenol, “Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and the ugly, ” Amer. J. Physiol., 271, 1424–1437 (1996).Google Scholar
  6. 6.
    G. W. Bergo and I. Tyssebotn, “Cerebral blood flow during exposure to 5 bar oxygen in awake rats, ” Undersea Biomed. Res., 19, 339–354 (1992).Google Scholar
  7. 7.
    G. Czapski and S. Goldstein, “The role of the reaction of NO with superoxide and oxygen in biological systems: a kinetic approach, ” Free Radic. Biol. Med., 19, 785–794 (1995).Google Scholar
  8. 8.
    I. T. Demchenko, A. E. Boso, M. J. Natoli, P. O. Doar, T. J. O'Neill, P. B. Bennett, and C. A. Piantadosi, “Measurement of cerebral blood flow in rats and mice by hydrogen clearance during hyperbaric oxygen exposure, ” Undersea Hyperbaric Med., 25, 147–153 (1998).Google Scholar
  9. 9.
    I. T. Demchenko, A. E. Boso, T. J. O'Neill, P. B. Bennett, and C. A. Piantadosi, “Nitric oxide and cerebral blood flow responses to hyperbaric oxygen, ” J. Appl. Physiol., 88, 1381–1389 (2000).Google Scholar
  10. 10.
    I. T. Demchenko, A. E. Boso, P. B. Bennett, A. R. Whorton, and C. A. Piantadosi, “Hyperbaric oxygen reduces cerebral blood flow by inactivating nitric oxide, ” Biology and Chemistry, 4, No. 6, 597–608 (2000).Google Scholar
  11. 11.
    A. Gibson and L. Elliot, “Superoxide anions, free radicals scavengers, and nitrergic neurotransmission, ” Gen. Pharmac., 28, 489–493 (1997).Google Scholar
  12. 12.
    R. J. Gryglewski, R. M. Palmer, and S. Moncada, “Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor, ” Nature, 320, 454–456 (1986).Google Scholar
  13. 13.
    C. Iadecola, D. D. Pelligrino, M. A. Moskowitz, and N. Lassen, “Nitric oxide synthase inhibition and cerebrovascular regulation, ” J. Cerebr. Blood Flow Metab., 14, 175–192 (1994).Google Scholar
  14. 14.
    I. Jacobson, A. M. Harper, and D. G. McDowall, “The effects of oxygen under pressure on cerebral blood flow and cerebral venous oxygen tension, ” Lancet, 2, 549–552 (1963).Google Scholar
  15. 15.
    A. S. Katusic, “Superoxide anion and endothelial regulation of arterial tone, ” Free Rad. Biol. Med., 20, 443–448 (1996).Google Scholar
  16. 16.
    C. J. Lambertsen, R. E. Krough, and D. Y. Cooper, “Oxygen toxicity. Effects in man of oxygen inhalation and 1 and 3.5 atmospheres upon blood gas transport, cerebral circulation and cerebral metabolism, ” J. Appl. Physiol., 5, 471–486 (1953).Google Scholar
  17. 17.
    J. R. Landcaster, Jr., “Simulation of the diffusion and reaction of endogenously produced nitric oxide, ” Proc. Natl. Acad. Sci. USA, 91, No. 17, 8137–8141 (1994).Google Scholar
  18. 18.
    B. Mayer and B. Hemmens, “Biosynthesis and action of nitric oxide in mammalian cells, ” TIBS, 22, 447–481 (1997).Google Scholar
  19. 19.
    T. Omae, S. Ibayashi, and K. Kusuda, “Effects of high atmospheric pressure and oxygen on middle cerebral blood flow velocity in humans measured by transcranial doppler, ” Stroke, 29, 94–97 (1997).Google Scholar
  20. 20.
    H. A. Omar, P. D. Cherry, and M. P. Mortelliti, “Inhibition of coronary artery superoxide dismutase attenuates endothelium-dependent and independent nitrovasodilator relaxation, ” Circ. Res., 69, 601–608 (1991).Google Scholar
  21. 21.
    T. D. Oury, B. J. Day, and J. D. Crapo, “Extracellular superoxide dismutase in vessels of humans and baboons, ” Free Rad. Biol. Med., 20, 957–965 (1966).Google Scholar
  22. 22.
    T. D. Oury, B. J. Day, and J. D. Crapo, “Extracellular superoxide dismutase: a regulator of nitric oxide bioavailability, ” Lab. Invest., 75, 617–636 (1966).Google Scholar
  23. 23.
    G. M. Rubanyi and P. M. Vanhoutte, “Superoxide dismutase and hyperoxia inactivate endothelium-dependent relaxing factor, ” Amer. J. Physiol., 250, H822–H8217 (1986).Google Scholar
  24. 24.
    J. S. Stamler, L. Jia, T. J. McMahon, I. T. Demchenko, J. Bonaventura, J. K. Gerent, and C. Piantadosi, “Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient, ” Science, 276, 2034–2037 (1996).Google Scholar
  25. 25.
    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).Google Scholar

Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • S. Yu. Zhilyaev
    • 1
  • A. N. Moskvin
    • 1
  • T. F. Platonova
    • 1
  • D. R. Gutsaeva
    • 1
  • I. V. Churilina
    • 2
  • I. T. Demchenko
    • 1
  1. 1.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of SciencesSt. PetersburgRussia
  2. 2.State Science Research Institute of High-Purity BiopreparationsSt. PetersburgRussia

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