Superoxide anions in the pathogenesis of talc-induced cerebral vasocontraction.
We have recently reported that sustained contraction of the canine basilar artery induced by the intrathecal injection of talc (crystallized hydrous magnesium silicate) mimicked delayed vasospasm following subarachnoid haemorrhage. The present study aims to examine the pathomechanism underlying talc-induced vasocontraction, from the viewpoint of free radical theory, which has been established as a cause of delayed vasospasm. We estimated the effects of a prolonged intrathecal infusion of human recombinant Cu/Zn superoxide dismutase (hr SOD) on the contraction of the basilar artery caused by the intrathecal injection of talc in beagle dogs, which were assigned to the three groups: G1, sham operation with saline treatment; G2, talc injection with saline treatment; and G3, talc injection with 2 ml of hr SOD (7 x 10(4) U/ml) treatment. Talc administration resulted in the reduction in the angiographic calibre of the basilar artery by 63 and 61% on days 3 and 7 (G2). The treatment with hr SOD (G3) led to a significant attenuation of talc-induced contraction of the basilar artery on days 3 (P < 0.05 vs. G2) and 7 (P < 0.05 vs. G2). In the basilar artery wall of days 3 and 7 in G2, pathological changes such as myonecrosis, cytoplasmic vacuolation and detached intercellular junctions were observed. However, these pathological changes almost disappeared in G3. The present findings suggest that superoxide anions may initiate and/or mediate talc-induced vasocontraction and subsequent structural damage of the basilar artery.
Mori
T
T
Division of Pathology, Nippon Medical School, Kanagawa, Japan.
Nagata
K
K
Matsui
T
T
Ishida
T
T
Ohami
H
H
Asano
T
T
D000818:Animals; D000838:Anions / Q000378:metabolism; D001488:Basilar Artery / Q000187:drug effects / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D002546:Ischemic Attack, Transient / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013627:Talc / Q000008:administration & dosage / Q000633:toxicity*; D014661:Vasoconstriction / Q000187:drug effects
D000838:Anions; D011994:Recombinant Proteins; D013481:Superoxides; D013627:Talc; D013482:Superoxide Dismutase