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.
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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).
A. G. Zhironkin, Oxygen. Physiological and Toxic Actions [in Russian], Nauka, Leningrad (1972).
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).
A. I. Selivra, Hyperbaric Oxygenation [in Russian], Nauka, Leningrad (1983).
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).
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).
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).
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).
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).
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).
A. Gibson and L. Elliot, “Superoxide anions, free radicals scavengers, and nitrergic neurotransmission, ” Gen. Pharmac., 28, 489–493 (1997).
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).
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).
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).
A. S. Katusic, “Superoxide anion and endothelial regulation of arterial tone, ” Free Rad. Biol. Med., 20, 443–448 (1996).
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).
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).
B. Mayer and B. Hemmens, “Biosynthesis and action of nitric oxide in mammalian cells, ” TIBS, 22, 447–481 (1997).
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).
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).
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).
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).
G. M. Rubanyi and P. M. Vanhoutte, “Superoxide dismutase and hyperoxia inactivate endothelium-dependent relaxing factor, ” Amer. J. Physiol., 250, H822–H8217 (1986).
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).
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).
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Zhilyaev, S.Y., Moskvin, A.N., Platonova, T.F. et al. Hyperoxic Vasoconstriction in the Brain Is Mediated by Inactivation of Nitric Oxide by Superoxide Anions. Neurosci Behav Physiol 33, 783–787 (2003). https://doi.org/10.1023/A:1025145331149
- nitric oxide
- superoxide anion
- brain blood flow
- hyperbaric oxygenation
- superoxide dismutase