Mechanism of Cerebral Vasospasm Induced by Oxyhaemoglobin

  • Y. Fujita
  • T. Shingu
  • H. Gi
  • O. Araki
  • M. Matsunaga
  • H. Handa


Vasocontractile responses to lytic products of erythrocytes have been well investigated (22, 23, 28, 29, 31) and these responses which are characteristically observed in the cerebral arteries are most strongly induced by oxyhaemoglobin (oxyHb), among other derivatives of haemoglobin (Hb) (9, 28, 29). However, the mechanism of the induction of oxyHb-induced contractile response on the vascular smooth muscle, especially in the cerebral arteries, remains unknown. Hb plays the physiological role of oxygen carrier in the biological system and Hb and its degradation products such as methaemoglobin (metHb), haematin, porphyrin and ferrous iron are important co-factors of enzymes which catalyze oxidation of polyunsaturated fatty acids (PUFAs), under experimental conditions (4, 20).


Linoleic Acid Electron Spin Resonance Cerebral Artery Electron Spin Resonance Spectrum Contractile Response 
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  1. 1.
    Asano, M., Hidaka, H.: Contractile response of isolated rabbit aortic strips to unsaturated fatty acid peroxides. Pharmacol. Exp. Ther. 3, 347–353 (1979)Google Scholar
  2. 2.
    Brabham, D.E., Lee, J.: Excited state interaction c -tocopherol and molecular oxygen. J. Phys. Chem. 80, 2292–2296 (1976)CrossRefGoogle Scholar
  3. 3.
    Brunori, M., Falcioni, G., Fioretti, E. et al.: Formation of superoxide in the autoxidation of the isolated and chains of human hemoglobin and its involvement in hemichrome precipitation. Eur. J. Biochem. 53, 99–104 (1975)CrossRefGoogle Scholar
  4. 4.
    Chan, H.W.-S., Newby, V.K., Levett, G.: Metal ion-catalysed oxidation of linoleic acid. Lipoxygenase-like regioselectivity of oxygenation. J.C.S. Chem. Comm. 82–83 (1978)Google Scholar
  5. 5.
    Chance, B., Sies, H., Boveris, A.: Hydroperoxide metabolism in mammalian organs. PhysioL Rev. 59, 527–605 (1979)PubMedGoogle Scholar
  6. 6.
    Chen, W.T., Brace, R.A., Scott, J.B. et al.: The mechanism of the vasodilator action of potassium. Proc. Soc. Exptl. Biol. Med. 140, 820–824 (1972)Google Scholar
  7. 7.
    De Groot, J.J., Veldink, G.A., Vliegenthart, J.F.G., et al.: Demonstration by EPR spectroscopy of the functional role of iron in soybean lipoxygenase-1. Biochim. Biophys. Acta 377, 71–79 (1975)Google Scholar
  8. 8.
    Fridovich, I.: The biology of oxygen radicals. Science 201, 875–880 (1978)PubMedCrossRefGoogle Scholar
  9. 9.
    Fujita, Y., Shingu, T., Yamada, K. et al.: Noxious free radicals derived from oxyhemoglobin as a cause of prolonged vasospasm. Neurologia. Med. Chir. 20, 137–144 (1980)CrossRefGoogle Scholar
  10. 10.
    Greenberg, S., Kadowitz, P.J., Long, J.P. et al.: Studies on the nature of a prostaglandin receptor in canine and rabbit vascular smooth muscle. Cir. Res. 39, 66–76 (1976)CrossRefGoogle Scholar
  11. 11.
    Ham, E.A., Egan, R.W., Soderman, D.D. et al.: Peroxidase-dependent deactivation of prostacyclin synthetase. J. Biol. Chem. 254, 2191–2194 (1979)PubMedGoogle Scholar
  12. 12.
    Hayaishi, O., Asada, K.: Biochemical and medical aspects of active oxygen. Tokyo: University Tokyo Press 1979Google Scholar
  13. 13.
    Huisman, P.H.J., Dozy, A.M.: Studies of the heterogeneity of hemoglobin. IX. J. Chromatogr. 19, 160–169 (1965)PubMedCrossRefGoogle Scholar
  14. 14.
    Janzen, E.G.: -A critical review of spin trapping in biological system. In: Free radicals in biology. Pryor, W.A. (ed.) pp. 115–154. New York: Academic Press 1980Google Scholar
  15. 15.
    Johnson, M., Jessup, R., Ramwell, P.W.: The significance of protein disulfide and sulfhydryl groups in prostaglandin action. Prostaglandin 5, 125–136 (1974)Google Scholar
  16. 16.
    Lockette, W.E., Webb, R.C., Bohr, D.F.: Prostaglandins and potassium relaxation in vascular smooth muscle of the rat. The role of Na-K-ATPase. Cir. Res. 46, 714–720 (1980)CrossRefGoogle Scholar
  17. 17.
    Matsuda, Y., Beppu, Y., Arima, K. et al.: Spin-state exchanges in fusarium lipoxygenase on binding of linoleic acid. Biochem. Biophys. Res. Commun. 86, 319–324 (1979)PubMedCrossRefGoogle Scholar
  18. 18.
    Matsuda, Y., Beppu, T., Arima, K.: Possible mechanism of oxygen activation in linoleate per-oxidation by fusarium lipoxygenase. Agric. Biol. Chem. 43, 1179–1186 (1979)CrossRefGoogle Scholar
  19. 19.
    Misra, M.P., Fridovich, I.: The generation of superoxide radical during the oxidation of hemoglobin. J. Biol. Chem. 247, 6960–6962 (1972)PubMedGoogle Scholar
  20. 20.
    Miyamoto, T., Ogino, N., Yamamoto, S. et al.: Purification of prostaglanding endoperoxide synthetase from bovine vesicular gland microsomes. J. Biol. Chem. 251, 2629–2636 (1976)PubMedGoogle Scholar
  21. 21.
    Moncada, S., Grygleski, R.J., Bunting, S.: A lipid peroxide inhibits the enzyme in blood vessel microsomes that generate from prostaglandin endoperoxides the substance (PGX) which prevents platelet aggregation. Prostaglandins 12, 715–737 (1979)Google Scholar
  22. 22.
    Osaka, K.: Prolonged vasospasm produced by the breakdown products of erythrocytes. J. Neurosurg. 47, 403–411 (1977)PubMedCrossRefGoogle Scholar
  23. 23.
    Ozaki, N., Mullan, S.: Possible role of the erythrocyte in causing prolonged cerebral vasospasm. J. Neurosurg. 51, 775–778 (1979)Google Scholar
  24. 24.
    Perutz, M.F.: Stereochemistry of cooperative effects in hemoglobin. Nature 228, 726–734 (1970)PubMedCrossRefGoogle Scholar
  25. 25.
    Rome, L.H., Lands, W.E.M.: Properties of a partially-purified preparation of the prostaglandin-forming oxygenase from sheep vesicular gland. Prostaglandins 10, 813–824 (1975)PubMedGoogle Scholar
  26. 26.
    Shingu, T., Fujita, Y., Handa, H. et al.: Intracranial hematomas and deleterious radicals derived from oxyhemoglobin. In: Ischemia and cell damage. Asano, T. (ed.), pp. 109–114. Tokyo: Nyuron Shya 1980Google Scholar
  27. 27.
    Siegel, M.E., McConnell, R.T., Abrahams, S.L., et al.: Regulation of arachidonate metabolism via lipoxygenase and cyclooxygenase by 12-HPETE. Biochm. Biophys. Res. Commun. 89, 12731280 (1979)Google Scholar
  28. 28.
    Sonobe, M., Suzuki, J.: Vasospasmogenic substance produced following subarachnoid haemorrhage, and its fate. Acta Neurochir. 44, 97–106 (1978)PubMedCrossRefGoogle Scholar
  29. 29.
    Tanishima, T.: Cerebral vasospasm: Contractile activity of hemoglobin in isolated canine basilar arteries. J. Neurosurg. 53, 787–793 (1980)PubMedCrossRefGoogle Scholar
  30. 30.
    Toda, N.: Responsiveness to potassium and calcium ions of isolated cerebral arteries. J. Physiol. 277, 1206–1211 (1974)Google Scholar
  31. 31.
    Toda, N., Shimizu, K., Ohta, T.: Mechanism of cerebral arterial contraction induced by blood constituents. J. Neurosurg. 53, 312–322 (1980)PubMedCrossRefGoogle Scholar
  32. 32.
    Weber, B., Oudega, B., Van Gelder, B.F.: Generation of superoxide radicals during the autoxidation of mammalian oxyhemoglobin. Biochim. Biophys. Acta 302, 475–478 (1973)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1982

Authors and Affiliations

  • Y. Fujita
  • T. Shingu
  • H. Gi
  • O. Araki
  • M. Matsunaga
  • H. Handa

There are no affiliations available

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