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+.
Zhang
A
A
Department of Physiology, State University of New York, Health Science Center at Brooklyn 11203, USA.
Cheng
T P
TP
Altura
B T
BT
Altura
B M
BM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002561:Cerebrovascular Disorders / Q000139:chemically induced / Q000503:physiopathology*; D015237:Dinoprost / Q000494:pharmacology*; D004285:Dogs; D000431:Ethanol / Q000494:pharmacology*; D005456:Fluorescent Dyes; D016257:Fura-2; D066298:In Vitro Techniques; D008297:Male; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*
D002492:Central Nervous System Depressants; D005456:Fluorescent Dyes; D000431:Ethanol; D015237:Dinoprost; D002118:Calcium; D016257:Fura-2