Contractile responses to reactive oxygen species in the canine basilar artery in vitro

Selective inhibitory effect of MCI-186, a new hydroxyl radical scavenger

Masahiko Tosaka, Y. Hashiba, N. Saito, H. Imai, T. Shimizu, T. Sasaki, T. Dóczi, A. Büki, V. Seifert

Research output: Article

34 Citations (Scopus)

Abstract

Background. Cerebral vasospasm is one of the important pathological phenomena which influence morbidity and mortality following subarachnoid haemorrhage. Reactive oxygen species (ROSs) generated by the autoxidation of oxyhemoglobin to methemoglobin may be one of the essential factors in the pathogenesis of cerebral vasospasm. The direct vasocontractile effects of hydrogen peroxide 3 (H2O2), superoxide anion (O2-), and hydroxyl radical (*OH) on the canine basilar artery and the inhibitory effects of MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one), a new *OH scavenger, were investigated. Method. Isometric tension was recorded in basilar artery rings from dogs in vitro. H2O2, pyrogallol (O2- donor), and vitamin C (VitC)/Fe2+ (*OH-generating system) were used to generate the ROSs. Findings. H2O2 (10 μmol/L), pyrogallol (10 μmol/L), and VitC/Fe2+ (100 μmol/L each) induced fast onset and transient, slow onset and transient, and sustained contraction, respectively, in the canine basilar artery. Contractions induced by H2O2 were almost completely inhibited by pre-incubation with catalase (800 U/mL) and those by pyrogallol with superoxide dismutase (150 U/mL), but neither with MCI-186 (10 μmol/L). The contraction induced by VitC/Fe2+ was clearly inhibited by pre-incubation with MCI-186, but not with catalase or superoxide dismutase. Interpretation. ROSs have direct vasocontractile effects on the canine basilar artery in vitro, but different ROSs have different contractile characteristics. Such contractions might be related to the pathophysiology of cerebral vasospasm. MCI-186 had a clear and selective inhibitory effect against *OH-induced contraction in vitro. Comparison of different radical scavengers may be important in pharmacological assessment, especially targeted on cerebral vasospasm.

Original languageEnglish
Pages (from-to)1305-1310
Number of pages6
JournalActa Neurochirurgica
Volume144
Issue number12
DOIs
Publication statusPublished - 2002

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Basilar Artery
Intracranial Vasospasm
Hydroxyl Radical
Canidae
Pyrogallol
Reactive Oxygen Species
Ascorbic Acid
Catalase
Superoxide Dismutase
Methemoglobin
Oxyhemoglobins
Subarachnoid Hemorrhage
Superoxides
Hydrogen Peroxide
phenylmethylpyrazolone
In Vitro Techniques
Pharmacology
Dogs
Morbidity
Mortality

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Contractile responses to reactive oxygen species in the canine basilar artery in vitro : Selective inhibitory effect of MCI-186, a new hydroxyl radical scavenger. / Tosaka, Masahiko; Hashiba, Y.; Saito, N.; Imai, H.; Shimizu, T.; Sasaki, T.; Dóczi, T.; Büki, A.; Seifert, V.

In: Acta Neurochirurgica, Vol. 144, No. 12, 2002, p. 1305-1310.

Research output: Article

Tosaka, Masahiko ; Hashiba, Y. ; Saito, N. ; Imai, H. ; Shimizu, T. ; Sasaki, T. ; Dóczi, T. ; Büki, A. ; Seifert, V. / Contractile responses to reactive oxygen species in the canine basilar artery in vitro : Selective inhibitory effect of MCI-186, a new hydroxyl radical scavenger. In: Acta Neurochirurgica. 2002 ; Vol. 144, No. 12. pp. 1305-1310.
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abstract = "Background. Cerebral vasospasm is one of the important pathological phenomena which influence morbidity and mortality following subarachnoid haemorrhage. Reactive oxygen species (ROSs) generated by the autoxidation of oxyhemoglobin to methemoglobin may be one of the essential factors in the pathogenesis of cerebral vasospasm. The direct vasocontractile effects of hydrogen peroxide 3 (H2O2), superoxide anion (O2-), and hydroxyl radical (*OH) on the canine basilar artery and the inhibitory effects of MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one), a new *OH scavenger, were investigated. Method. Isometric tension was recorded in basilar artery rings from dogs in vitro. H2O2, pyrogallol (O2- donor), and vitamin C (VitC)/Fe2+ (*OH-generating system) were used to generate the ROSs. Findings. H2O2 (10 μmol/L), pyrogallol (10 μmol/L), and VitC/Fe2+ (100 μmol/L each) induced fast onset and transient, slow onset and transient, and sustained contraction, respectively, in the canine basilar artery. Contractions induced by H2O2 were almost completely inhibited by pre-incubation with catalase (800 U/mL) and those by pyrogallol with superoxide dismutase (150 U/mL), but neither with MCI-186 (10 μmol/L). The contraction induced by VitC/Fe2+ was clearly inhibited by pre-incubation with MCI-186, but not with catalase or superoxide dismutase. Interpretation. ROSs have direct vasocontractile effects on the canine basilar artery in vitro, but different ROSs have different contractile characteristics. Such contractions might be related to the pathophysiology of cerebral vasospasm. MCI-186 had a clear and selective inhibitory effect against *OH-induced contraction in vitro. Comparison of different radical scavengers may be important in pharmacological assessment, especially targeted on cerebral vasospasm.",
keywords = "Canine basilar artery, MCI-186, Reactive oxygen species, Subarachnoid haemorrhage",
author = "Masahiko Tosaka and Y. Hashiba and N. Saito and H. Imai and T. Shimizu and T. Sasaki and T. D{\'o}czi and A. B{\"u}ki and V. Seifert",
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T1 - Contractile responses to reactive oxygen species in the canine basilar artery in vitro

T2 - Selective inhibitory effect of MCI-186, a new hydroxyl radical scavenger

AU - Tosaka, Masahiko

AU - Hashiba, Y.

AU - Saito, N.

AU - Imai, H.

AU - Shimizu, T.

AU - Sasaki, T.

AU - Dóczi, T.

AU - Büki, A.

AU - Seifert, V.

PY - 2002

Y1 - 2002

N2 - Background. Cerebral vasospasm is one of the important pathological phenomena which influence morbidity and mortality following subarachnoid haemorrhage. Reactive oxygen species (ROSs) generated by the autoxidation of oxyhemoglobin to methemoglobin may be one of the essential factors in the pathogenesis of cerebral vasospasm. The direct vasocontractile effects of hydrogen peroxide 3 (H2O2), superoxide anion (O2-), and hydroxyl radical (*OH) on the canine basilar artery and the inhibitory effects of MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one), a new *OH scavenger, were investigated. Method. Isometric tension was recorded in basilar artery rings from dogs in vitro. H2O2, pyrogallol (O2- donor), and vitamin C (VitC)/Fe2+ (*OH-generating system) were used to generate the ROSs. Findings. H2O2 (10 μmol/L), pyrogallol (10 μmol/L), and VitC/Fe2+ (100 μmol/L each) induced fast onset and transient, slow onset and transient, and sustained contraction, respectively, in the canine basilar artery. Contractions induced by H2O2 were almost completely inhibited by pre-incubation with catalase (800 U/mL) and those by pyrogallol with superoxide dismutase (150 U/mL), but neither with MCI-186 (10 μmol/L). The contraction induced by VitC/Fe2+ was clearly inhibited by pre-incubation with MCI-186, but not with catalase or superoxide dismutase. Interpretation. ROSs have direct vasocontractile effects on the canine basilar artery in vitro, but different ROSs have different contractile characteristics. Such contractions might be related to the pathophysiology of cerebral vasospasm. MCI-186 had a clear and selective inhibitory effect against *OH-induced contraction in vitro. Comparison of different radical scavengers may be important in pharmacological assessment, especially targeted on cerebral vasospasm.

AB - Background. Cerebral vasospasm is one of the important pathological phenomena which influence morbidity and mortality following subarachnoid haemorrhage. Reactive oxygen species (ROSs) generated by the autoxidation of oxyhemoglobin to methemoglobin may be one of the essential factors in the pathogenesis of cerebral vasospasm. The direct vasocontractile effects of hydrogen peroxide 3 (H2O2), superoxide anion (O2-), and hydroxyl radical (*OH) on the canine basilar artery and the inhibitory effects of MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one), a new *OH scavenger, were investigated. Method. Isometric tension was recorded in basilar artery rings from dogs in vitro. H2O2, pyrogallol (O2- donor), and vitamin C (VitC)/Fe2+ (*OH-generating system) were used to generate the ROSs. Findings. H2O2 (10 μmol/L), pyrogallol (10 μmol/L), and VitC/Fe2+ (100 μmol/L each) induced fast onset and transient, slow onset and transient, and sustained contraction, respectively, in the canine basilar artery. Contractions induced by H2O2 were almost completely inhibited by pre-incubation with catalase (800 U/mL) and those by pyrogallol with superoxide dismutase (150 U/mL), but neither with MCI-186 (10 μmol/L). The contraction induced by VitC/Fe2+ was clearly inhibited by pre-incubation with MCI-186, but not with catalase or superoxide dismutase. Interpretation. ROSs have direct vasocontractile effects on the canine basilar artery in vitro, but different ROSs have different contractile characteristics. Such contractions might be related to the pathophysiology of cerebral vasospasm. MCI-186 had a clear and selective inhibitory effect against *OH-induced contraction in vitro. Comparison of different radical scavengers may be important in pharmacological assessment, especially targeted on cerebral vasospasm.

KW - Canine basilar artery

KW - MCI-186

KW - Reactive oxygen species

KW - Subarachnoid haemorrhage

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