Reactive oxygen species and acute modulation of albumin microvascular leakage in the microcirculation of diabetic rats in vivo.
Endothelial cells have been reported to generate reactive oxygen species such as the superoxide anion, hydrogen peroxide, and the hydroxyl radical. The aim of this work was to evaluate the role of reactive oxygen species in diabetes-induced changes in vascular permeability. Intravital videomicroscopy was used to study albumin microvascular leakage in the cremaster muscle. The extravasation of a fluorescent macromolecular tracer (FITC-albumin) was measured for 1 h and, after computer-aided image analysis, was expressed as variations of normalized gray levels (arbitrary units). The extravasation of the macromolecular tracer was greater in diabetic rats (5.28 +/- 1.29 vs. 1.96 +/- 0.41 AU at 1 h in diabetic and control rats, respectively). Administration of superoxide dismutase (SOD), which dismutates.O(-)(2) to H(2)O(2), and of catalase which reacts with H(2)O(2) to form H(2)O and molecular oxygen failed to inhibit the increased extravasation of the macromolecular tracer when administered separately. However, a significant inhibition of diabetic increase in albumin extravasation was found when these 2 drugs were administered simultaneously, and in this case, the extravasation of the macromolecular tracer at 1 h was similar in diabetic rats (2.11 +/- 0.61 AU) and normoglycemic rats (1.43 +/- 0. 48 AU). No difference was found in adherent leukocytes or in the leukocyte rolling flux between diabetic and normoglycemic rats. We conclude that reactive oxygen species are responsible for an increase in microvascular permeability likely via leukocyte-independent mechanisms.
Bonnardel-Phu
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Microvascular Research Laboratory, Département of Biophysics, F. Widal Hospital, Paris, France.
Vicaut
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D000418:Albumins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002196:Capillaries / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D002374:Catalase / Q000494:pharmacology; D002448:Cell Adhesion; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005119:Extravasation of Diagnostic and Therapeutic Materials; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000502:physiology*; D013482:Superoxide Dismutase / Q000494:pharmacology
D000418:Albumins; D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase; D016650:Fluorescein-5-isothiocyanate