Staurosporine and H7 attenuate ethanol-induced elevation in [Ca2+]i in cultured canine cerebral vascular smooth muscle cells.

Chronic exposure of cultured canine cerebral vascular smooth muscle cells to ethanol (10-400 mM) for 1-5 days resulted in significant concentration-dependent elevation in resting intracellular free calcium ([Ca2+]i) levels. Preincubation of these cultured vascular cells with inhibitors of protein kinase C (PKC), staurosporine and H7, induced no apparent changes from the control resting levels of [Ca2+]i. However, the increases of [Ca2+]i due to ethanol treatment were attenuated markedly by staurosporine and H7. Our data suggest that activation of PKC plays an important role in ethanol's action in producing a sustained rise in [Ca2+]i in cerebral vascular smooth muscle cells. Activation of PKC could thus play a crucial role in the pathogenesis of alcohol-induced cerebral ischemia and stroke.