Chronic treatment of cultured cerebral vascular smooth cells with low concentration of ethanol elevates intracellular calcium and potentiates prostanoid-induced rises in [Ca2+]i: relation to etiology of alcohol-induced stroke.

The influence of chronic treatment of cultured canine cerebral vascular smooth muscle cells, with low concentrations of ethanol, on the intracellular concentrations of free calcium ([Ca2+]i) was studied by use of the fluorescent indicator, fura-2, and digital imaging microscopy. The resting level of [Ca2+]i in the cerebral vascular smooth muscle cells was 89 +/- 3.2 nM. Exposure of these cells to 10 and 25 mM ethanol for 5 days resulted in significant elevation of [Ca2+]i (mean rises to 208 +/- 11.4 and 307 +/- 14.0 nM, respectively), and potentiated the transient rise in [Ca2+]i induced by 10(-7) M PGF2 alpha. However, exposure of these cerebral cells to a high-concentration ethanol (100 mM) resulted in only a slight increase of [Ca2+]i (106 +/- 6.9 nM) and lack of effects on the [Ca2+]i response to PGF2 alpha. Irrespective of the different ethanol treatments, the subcellular distribution of [Ca2+]i was heterogeneous in all the cells tested. Our data suggest that chronic exposure of cerebral vascular smooth muscle cells to ethanol, particularly at low concentrations, results in dramatic increases in [Ca2+]i and the responses of these vascular smooth muscle cells to prostanoids. These results support an hypothesis whereby ethanol induces stroke by causing spasm and rupture of cerebral blood vessels as a consequence of large rises in intracellular Ca2+.