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.
Tanaka
Y
Y
Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Ishiro
H
H
Nakazawa
T
T
Saito
M
M
Ishii
K
K
Nakayama
K
K
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism*; D004285:Dogs; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D016257:Fura-2; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D010738:Type C Phospholipases / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D016232:Endothelins; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D010738:Type C Phospholipases; D002118:Calcium; D016257:Fura-2; D007213:Indomethacin