Superoxide dismutase as an inhibitor of postischemic microvascular permeability increase in the hamster.
The purpose was to elucidate the involvement of superoxide radical (O2-.) in the postischemic increase in the vascular permeability in the hamster cheek pouch. Cheek pouches of anesthetized hamsters were everted, prepared for intravital microscopy, and superfused with a bicarbonate buffered saline solution. Local ischemia for 30 min was obtained using a cuff placed around the proximal part of the cheek pouch. The vascular permeability in the postcapillary venules was quantified as leakage of intravenously injected fluorescein labeled dextran (FITC-dextran, Mw 150,000), using intravital microscopy and fluorimetry. There was a significant and reversible permeability increase after the reperfusion started. In the first series of experiments, combined intravenous infusion and topical application of human recombinant extracellular superoxide dismutase C (EC-SOD C) reduced the postischemic permeability response by 80%. Bovine CuZn-SOD given in exactly the same way reduced the response by 60%. In the second series of experiments, inactivated EC-SOD C was given to the control animals and active EC-SOD C was given to the treated animals. The topical treatment was excluded. Only active EC-SOD C reduced significantly the postischemic permeability increase when present during the ischemic period. Treatment with mannitol (i.v.) did not alter the postischemic response. Since active EC-SOD C and CuZn-SOD but not inactivated EC-SOD C effectively inhibited the response, we suggest that the superoxide anion is involved in the mediation of the postischemic permeability increase in the hamster.
Erlansson
M
M
Department of Pharmacology, AB Draco, Lund, Sweden.
Bergqvist
D
D
Marklund
S L
SL
Persson
N H
NH
Svensjö
E
E
D000818:Animals; D002560:Cerebrovascular Circulation; D002610:Cheek; D006224:Cricetinae; D005609:Free Radicals; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D015427:Reperfusion Injury / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000097:blood / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D007527:Isoenzymes; D013481:Superoxides; D013482:Superoxide Dismutase