Role of xanthine oxidase in postischemic microvascular injury in skeletal muscle.
Previous reports indicate that allopurinol, a xanthine oxidase inhibitor, attenuates the microvascular injury produced by reperfusion of ischemic skeletal muscle. To further assess the role of xanthine oxidase in ischemia/reperfusion (I/R) injury, we examined the effect of xanthine oxidase depletion or inhibition on the increase in microvascular permeability produced by I/R. Changes in vascular permeability were assessed by measurement of the solvent drag reflection coefficient for total plasma proteins (sigma) in rat hindquarters subjected to 2 h of ischemia and 30 min of reperfusion in xanthine oxidase-replete and -depleted animals and in animals pretreated with the xanthine oxidase inhibitor oxypurinol. Xanthine oxidase depletion was accomplished by administration of a tungsten-supplemented (0.7 g/kg diet), molybdenum-deficient diet. In animals fed the tungsten diet, muscle total xanthine dehydrogenase plus xanthine oxidase activity was decreased to less than 10% of control values. Estimates of sigma averaged 0.85 +/- 0.04 in nonischemic (continuous perfusion for 2.5 h) hindquarters, whereas muscle xanthine oxidase activity averaged 3.3 +/- 0.4 mU/g wet wt. I/R was associated with a marked decrease in sigma (0.54 +/- 0.02), whereas xanthine oxidase activity was increased to 5.8 +/- 0.5 mU/g wet wt. These results indicate that I/R produced a dramatic increase in vascular permeability coincident with an increase in muscle xanthine oxidase activity. Xanthine oxidase depletion with the tungsten diet or pretreatment with oxypurinol attenuated this permeability increase (sigma = 0.72 +/- 0.03 and 0.77 +/- 0.7, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Smith
J K
JK
Department of Physiology and Biophysics, Louisiana State University Medical Center, School of Medicine, Shreveport 71130.
Carden
D L
DL
Korthuis
R J
RJ
D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D002199:Capillary Permeability; D007511:Ischemia / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D009132:Muscles / Q000098:blood supply* / Q000201:enzymology / Q000503:physiopathology; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012039:Regional Blood Flow; D013481:Superoxides / Q000097:blood; D014655:Vascular Resistance; D014969:Xanthine Oxidase / Q000378:metabolism*
D001798:Blood Proteins; D013481:Superoxides; D014969:Xanthine Oxidase