Endothelium-dependent calcium-induced relaxation in the presence of Ca2+-antagonists in canine depolarized coronary arteries.
1. We examined the mechanisms underlying Ca2+-induced relaxation in the presence of clentiazem, a new Ca2+-antagonist, in depolarized coronary arteries of the dog. 2. Ca2+ (3 x 10(-5)-3 x 10(-3) M) caused an unexpected relaxation in the presence of a high concentration of clentiazem (10(-6) M) in coronary, but not in mesenteric or renal arteries. 3. The Ca2+-induced relaxation was also observed in the presence of established Ca2+-antagonists such as diltiazem (3 x 10(-6) M), nifedipine (3 x 10(-8) M) and verapamil (3 x 10(-6) M). 4. The Ca2+-induced relaxation was inhibited by removal of the endothelium, treatment with oxyhaemoglobin (1.5 x 10(-6) M) or methylene blue (10(-5) M), but not by treatment with indomethacin (5 x 10(-6) M). 5. The Ca2+-induced relaxation was observed in an endothelium-denuded coronary artery segment when closely apposed to an endothelium-containing segment of coronary or mesenteric artery. 6. These results suggest that Ca2+-induced relaxation in the presence of high concentrations of Ca2+-antagonists is mediated through endothelium-derived relaxing factor (EDRF). In addition, Ca2+-antagonists do not affect the Ca2+-influx necessary for the release and/or synthesis of EDRF.
Kikkawa
K
K
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Murata
S
S
Nagao
T
T
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000494:pharmacology
D002121:Calcium Channel Blockers; D009467:Neuromuscular Depolarizing Agents; D010108:Oxyhemoglobins; D002118:Calcium; D008751:Methylene Blue; D007213:Indomethacin