Dexamethasone prevents the microcirculatory inflammatory response to systemic hypoxia

摘要

Dexamethasone is effective in the treatment of AMS, suggesting the involvement of an inflammatory component in this condition. We have shown that systemic hypoxia produces an inflammatory response characterized by increases in reactive oxygen species (ROS) generation, leukocyte-endothelial adhesive interactions, and vascular permeability in various microcirculatory beds of rats. The objective of this study was to determine if dexamethasone prevents these responses. The mesenteric microcirculation of rats was studied using intravital microscopy. Hypoxia (FI02 = 0.10) increased the number of leukocytes adhering to venules (leukocytes / 100 mum) from 0.5+- 0.2 in normoxia to 10.7 +- 0.7 after 10 min of hypoxia (p< 0.05). This was accompanied by a 61 +- 10 % increase (p<0.05) in the fluorescence intensity of dyhydrorhodamine (DHR), an ROS probe. Pretreatment with dexamethasone (2 mg / kg subcutaneously 24 h before hypoxia) completely blocked the increase in leukocyte adherence and in DHR fluorescence. These results indicate that dexamethasone prevents the inflammatory response to hypoxia in the mesenteric microcirculation and suggest that its effect on AMS may involve its anti-inflammatory properties.