The present study investigated the effect of cytotoxic
hypoxia on cerebral and non-cerebral endothelial cells.
Hypoxia was induced by inhibiting the cellular respiratory chain with 1 mM
sodium cyanide. Cerebral endothelial cells were damaged after 2 h of
hypoxia as assessed by a decrease in cell viability by 25% and by a 2.7-fold higher
lactate dehydrogenase release compared to controls. Additional
glucose deprivation did not significantly exacerbate hypoxic injury. In addition, we found after 2 h of
hypoxia an increase in the release of
lactate of 1.02 and 0.42 mg/mg
protein compared to 0.27 and 0.07 mg/mg
protein in controls in the presence and absence of
glucose, respectively. While the activity of ALP of cerebral endothelial cells was maintained at the control level, we found a significant decrease in the gamma-GT activity from 3.8 +/- 1.3 to 1.09 +/- 0.3 U/mg
protein after 3 h of
hypoxia in the presence as well as in the absence of
glucose. The paracellular permeability of the cell monolayer decreased after 1 h and returned to control level after 3 h of
hypoxia in the presence of
glucose. Non-cerebral endothelial cells remained 98% viable with no change in the release of
lactate dehydrogenase and
lactate after 2 h of
hypoxia in the presence and absence of
glucose. The activities of ALP and gamma-GT in non-cerebral endothelial cells were 10 and 3 times lower and remained unchanged during
hypoxia. We conclude from our experiments that
sodium cyanide is useful to study hypoxic injury and that cerebral endothelial cells are more sensitive than non-cerebral endothelial cells to cytotoxic
hypoxia.