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 Ca(2+)-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.