Systemic hypoxia promotes leukocyte-endothelial adherence via reactive oxidant generation

We recently demonstrated that systemic hypoxia during reduced inspired Po-2 produces a rapid increase in leukocyte adherence to rat mesenteric venules . Evidence suggests that the mechanism of this response involves decreased nitric oxide (NO) levels. One possible pathway for NO depletion could invol ve increased reactive oxygen species (ROS) generation resulting in inactiva tion of NO. The overall goal of the present study was to examine the role o f ROS in promoting leukocyte-endothelial adherence during systemic hypoxia. Experiments were designed to 1) evaluate changes in ROS generation in the mesenteric microcirculation during systemic hypoxia, 2) determine how the R OS signal changes when Po-2 levels return to normal after a period of syste mic hypoxia, 3) assess the effect of antioxidants on ROS generation during hypoxia, and 4) utilize antioxidants to examine the functional relationship between ROS generation and leukocyte adherence during hypoxia. The major f indings from this study are that systemic hypoxia increases ROS generation within the mesenteric microcirculation and that antioxidants prevent the in crease in leukocyte-endothelial adhesive interactions observed in hypoxia.