POTENTIATION BY ENDOTHELIN-1 OF CA2+ SENSITIVITY OF CONTRACTILE ELEMENTS DEPENDS ON CA2+ INFLUX THROUGH L-TYPE CA2+ CHANNELS IN THE CANINE CEREBRAL-ARTERY

1. Endothelin-1 (ET-1) contracted canine cerebral artery in a concentration-dependent manner with an increase in intracellular Ca2+ concentration ([Ca2+](i)), and at higher concentrations it produced a greater contraction with a smaller increase in [Ca2+](i). 2. Ca2+ channel antagonist such as d-cis-diltiazem inhibited the tension more effectively than the [Ca2+](i) increased by ET-1. 3. In Ca2+-free solution containing 0.2 mM EGTA, ET-1 elicited a transient increase in [Ca2+](i) and tension. 4. In the Staphylococcus aureus alpha-toxin-permeabilized artery, ET-1 shifted the pCa-tension relationship leftwards in the presence of GTP. 5. These findings suggest that ET-1 contracts the canine cerebral artery by increasing not only the Ca2+ influx through L-type Ca2+ channels, but also Ca2+ release from the intracellular storage sites, and also Ca2+ sensitivity of contractile elements. The degree of Ca2+ sensitivity is strongly affected by [Ca2+](i) which is increased by the Ca2+ influx through L-type Ca2+ channels.