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 su ch as the superoxide anion, hydrogen peroxide, and the hydroxyl radical. Th e aim of this work was to evaluate the role of reactive oxygen species in d iabetes-induced changes in vascular permeability. Intravital videomicroscop y 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 a s variations of normalized gray levels (arbitrary units). The extravasation of the macromolecular tracer was greater in diabetic rats (5.28 +/- 1.29 v s. 1.96 +/- 0.41 AU at 1 h in diabetic and control rats, respectively). Adm inistration of superoxide dismutase (SOD), which dismutates O-.(2)- to H2O2 , and of catalase which reacts with H2O2 to form H2O and molecular oxygen f ailed to inhibit the increased extravasation of the macromolecular tracer w hen administered separately. However, a significant inhibition of diabetic increase in albumin extravasation was found when these 2 drugs were adminis tered simultaneously, and in this case, the extravasation of the macromolec ular tracer at 1 h was similar in diabetic rats (2.11 +/- 0.61 AU) and norm oglycemic rats (1.43 +/- 0.48 AU). No difference was found in adherent leuk ocytes or in the leukocyte rolling flux between diabetic and normoglycemic rats. We conclude th at reactive oxygen species are responsible for an incr ease in microvascular permeability likely via leukocyte-independent mechani sms. Copyright (C) 2000 S. Karger AG, Basel.