TY - JOUR
T1 - Antioxidants attenuate endotoxin-induced microvascular leakage of macromolecules in vivo
AU - Matsuda, T.
AU - Eccleston, C. A.
AU - Rubinstein, I.
AU - Rennard, S. I.
AU - Joyner, W. L.
PY - 1991
Y1 - 1991
N2 - The purpose of this study was to examine whether antioxidants attenuate endotoxin-induced microvascular hyperpermeability for macromolecules in the hamster cheek pouch. Twenty-two adult male Syrian hamsters were anesthetized, and a removable plastic chamber was placed in the cheek pouch to observe and collect suffusate from the microvasculature. Fluorescent-labeled dextran (FITC-D; mol wt 150,000) was injected intravenously, and changes in the number of microvascular leaky sites and microvascular clearance of FITC-D were measured in five groups: saline control (group 1, n = 4), endotoxin (0.1 mg/ml) suffusion for 120 min (group 2, n = 6), endotoxin plus dimethyl sulfoxide (1.0 g/kg iv; group 3, n = 4), endotoxin plus allopurinol (30 mg/kg ip; group 4, n = 4), and endotoxin plus dimethyl sulfoxide and allopurinol (group 5, n = 4). The number of leaky sites and the FITC-D clearance were significantly higher in group 2 [45 ± 18 (SD) sites/cm2 and 20 ± 6 x 10-6 ml/min, respectively; P < 0.01] than in group 1 (7 ± 6 sites/cm2 and 7 ± 5 x 10-6 ml/min), group 3 (9 ± 5 sites/cm2 and 8 ± 2 x 10-6 ml/min), group 4 (11 ± 7 sites/cm2 and 9 ± 4 x 10-6 ml/min), and group 5 (11 ± 6 sites/cm2 and 7 ± 1 x 10-6 ml/min). The leaky sites appeared predominantly in postcapillary venules. There was a positive and significant correlation between the number of leaky sites and FITC-D clearance. We conclude that endotoxin-mediated microvascular injury in vivo is associated with an acute increase in the number of leaky sites and microvascular clearance of macromolecules from the systemic circulation and that antioxidants attenuate these effects. We suggest that oxygen free radicals have a major role in the pathogenesis of endotoxin-mediated microvascular injury in vivo.
AB - The purpose of this study was to examine whether antioxidants attenuate endotoxin-induced microvascular hyperpermeability for macromolecules in the hamster cheek pouch. Twenty-two adult male Syrian hamsters were anesthetized, and a removable plastic chamber was placed in the cheek pouch to observe and collect suffusate from the microvasculature. Fluorescent-labeled dextran (FITC-D; mol wt 150,000) was injected intravenously, and changes in the number of microvascular leaky sites and microvascular clearance of FITC-D were measured in five groups: saline control (group 1, n = 4), endotoxin (0.1 mg/ml) suffusion for 120 min (group 2, n = 6), endotoxin plus dimethyl sulfoxide (1.0 g/kg iv; group 3, n = 4), endotoxin plus allopurinol (30 mg/kg ip; group 4, n = 4), and endotoxin plus dimethyl sulfoxide and allopurinol (group 5, n = 4). The number of leaky sites and the FITC-D clearance were significantly higher in group 2 [45 ± 18 (SD) sites/cm2 and 20 ± 6 x 10-6 ml/min, respectively; P < 0.01] than in group 1 (7 ± 6 sites/cm2 and 7 ± 5 x 10-6 ml/min), group 3 (9 ± 5 sites/cm2 and 8 ± 2 x 10-6 ml/min), group 4 (11 ± 7 sites/cm2 and 9 ± 4 x 10-6 ml/min), and group 5 (11 ± 6 sites/cm2 and 7 ± 1 x 10-6 ml/min). The leaky sites appeared predominantly in postcapillary venules. There was a positive and significant correlation between the number of leaky sites and FITC-D clearance. We conclude that endotoxin-mediated microvascular injury in vivo is associated with an acute increase in the number of leaky sites and microvascular clearance of macromolecules from the systemic circulation and that antioxidants attenuate these effects. We suggest that oxygen free radicals have a major role in the pathogenesis of endotoxin-mediated microvascular injury in vivo.
KW - blood vessels
KW - hamster
KW - microvascular clearance
KW - oxygen free radicals
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U2 - 10.1152/jappl.1991.70.4.1483
DO - 10.1152/jappl.1991.70.4.1483
M3 - Article
C2 - 1711521
AN - SCOPUS:0025757262
VL - 70
SP - 1483
EP - 1489
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
SN - 0161-7567
IS - 4
ER -