| Research Abstract |
Kinetic analysis using long acting and endothelially targeted superoxide dismutase (SOD) revealed that superoxide and related reactive oxygen species play important role in the pathogenesis of vasogenic tissue injury. Hence, selective dismutation of superoxide radicals is of critical importance in preventing and/or treating patients with circulatory disturbance. Targeting SOD to mannose-receptor-containing cells resulted inn rapid decrease in blood pressure, suggesting that the receprot-containing cells are responsible for the maintenance of blood pressure. Biochemical analysis using radiolabeled mannose-linked SOD revealed that more than 90% of SOD was localized in hepatic Kupffer cells and splenic macrophages. However, splenolectomy and 75% hepatectomy did not affect the depressor action of SOD,suggesting that other tissue (s) than liver and spleen might be responsible for the maintenance of the circulatory status. Kinetic analysis using various anesthetics, atropine and guanethidine suggested that the mannose receptor containing cells might localize in central nervous system. Specific antibody against mannose-linked SOD and mannose-linked xanthine oxidase might permit studies on the determination of the receptor-containing cells in the brain and on the mechanism by which circulatory status is regulated by cross-talk of reactive oxygen species.
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