DIRECT AND ASTROCYTE-MEDIATED EFFECTS OF ETHANOL ON DRAIN-DERIVED ENDOTHELIAL-CELLS

The effects of ethanol have been studied in the central nervous system , however there exists only scarce information about the effects of et hanol on endothelial cells forming the blood-brain barrier. As some pr operties of brain endothelial cells are modulated by underlying astroc ytes, the effect of ethanol on cerebral microvasculature might be indi rect and mediated by astrocytes. To analyse this question we added to rat brain-derived endothelial cells (rbEC) in culture either only etha nol (0, 15 and 150 mM) or ethanol conjointly with soluble factor secre ted by astrocytes. Alternatively, astrocytes were exposed to ethanol a nd the medium was added to rbEC. The effects of treatments were evalua ted on cell growth and expression of specific proteolytic markers of r bEC. The experiments showed that while the addition of ethanol alone t o rbEC increased the expression of gamma-glutamyltranspeptidase and ce ll growth following an initial toxic effect, the most significant effe cts were seen when ethanol was added to rbEC together with astrocytic factors or when medium conditioned by astrocytes exposed to ethanol wa s added to rbEC. In particular, the expression of angiotensin converti ng enzyme in endothelial cells was dose-dependently increased. These r esults indicate that the hypertensive and toxic effects of ethanol are mediated by ethanol and soluble factor(s) secreted by astrocytes and dependent on the expression of angiotensin converting enzyme in the br ain endothelium. Thus, when evaluating in vitro the effects of toxic s ubstances such as ethanol on the cerebral endothelium, the modulating effect of cells surrounding cerebral vessels must be accounted for.