BARBITURATES DECREASE THE EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR IN HYPOXIC CULTURES OF PORCINE BRAIN-DERIVED MICROVASCULAR ENDOTHELIAL-CELLS
S. Fischer et al., BARBITURATES DECREASE THE EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR IN HYPOXIC CULTURES OF PORCINE BRAIN-DERIVED MICROVASCULAR ENDOTHELIAL-CELLS, Molecular brain research, 60(1), 1998, pp. 89-97
Vascular endothelial growth factor (VEGF) is known to be produced in h
igher amounts during hypoxia by a variety of cell types and has been s
hown to increase the permeability of brain derived microvascular endot
helial cells (BMEC) during hypoxia by an autocrine mechanism. Because
the barbiturates, methohexital (MH) and thiopental (TP), induced a dos
e-dependent reduction in hypoxia-induced permeability changes of BMEC,
the effect of both barbiturates on the VEGF expression during hypoxia
was investigated. Both barbiturates decreased the hypoxia-induced exp
ression of VEGF in BMEC in a concentration-dependent manner. This effe
ct is partly caused by the impairment of the hypoxia-induced VEGF mRNA
stabilization. VEGF-induced permeability changes during normoxia were
unaffected by the barbiturates suggesting that MH and TP are directly
reducing hypoxia-induced VEGF synthesis. In conclusion, the inhibitin
g effect of these barbiturates on the hypoxia-induced VEGF expression
results in the decreased permeability of the BMEC monolayer during hyp
oxia, which may contribute to the described neuroprotective action of
barbiturates by reduction of brain edema formation. (C) 1998 Elsevier
Science B.V. All rights reserved.