Importance of extracellular Ca2+ and intracellular Ca2+ release in ethanol-induced contraction of cerebral arterial smooth muscle

The present study was designed to investigate the roles of extracellular Ca2+ ([Ca2+](0)) influx and intracellular free Ca2+ ([Ca2+](i)) release in ethanol-induced contractions of isolated canine cerebral arteries and primary cultured, cerebral vascular smooth muscle cells. Ethanol (20-200 mM) produced significant contractions in isolated canine basilar arterial rings in a concentration-dependent manner. Removal of [Ca2+](0) and pretreatment of canine basilar arterial rings with verapamil (an antagonist of voltage-gated Ca2+ channels), thapsigargin (a selective antagonist of the sarcoplasmic reticulum Ca2+ pump), caffeine plus ryanodine (a specific antagonist of ryanodine-sensitive Ca2+ release), or heparin (an inositol 1,4,5,-trisphosphate [InsP(3)]-mediated Ca2+ release antagonist) markedly attenuated (-50%-80%) ethanol-induced contractions. The absence of [Ca2+](0) and preincubation of primary single smooth muscle cells obtained from canine basilar arteries with verapamil, thapsigargin, heparin, or caffeine plus ryanodine markedly attenuated (-50%-80%) the transient and sustained elevations in [Ca2+](i) induced by ethanol. Results of the present study suggest to us that both Ca2+ influx through voltage-gated Ca2+ channels and Ca2+ release from intracellular stores (both InsP(3) sensitive and ryanodine sensitive) are required for ethanol-induced contractions of isolated canine basilar arteries. (C) 2001 Elsevier Science Inc. All rights reserved.