Contractile Responses to Reactive Oxygen Species in the Canine Basilar Artery in Vitro: Selective Inhibitory Effect of MCI-186, a new Hydroxyl Radical Scavenger

Summary.

 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 (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.