Mechanism of endothelium-dependent relaxation induced by thrombin in the pig coronary artery.
The mechanism of thrombin-induced endothelium-dependent relaxation was investigated using fura-2 front-surface fluorometry. Thrombin induced an endothelium-dependent relaxation during U46619-induced contractions in pig coronary arterial strips. The relaxation consisted of two components: the early phasic component with a transient decrease in [Ca2+]i of smooth muscle and the subsequent sustained tonic component without [Ca2+]i decrease. The phasic relaxation was inhibited by a combination of N(omega)-nitro-L-arginine and K+-depolarization, while the tonic component was inhibited by either indomethacin or K+-depolarization. Thrombin induced a transient [Ca2+]i increase and nitric oxide (NO) production in pig aortic valvular endothelial cells, which expressed NO synthase as determined by reverse transcription and polymerase chain reaction. Thus, it was concluded that NO and hyperpolarizing factor were involved in the phasic component of thrombin-induced relaxation and that hyperpolarizing factor and prostacyclin were involved in the tonic component.
Division of Molecular Cardiology, Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
O
O
Mizuno
K
K
Hirano
J
J
Nishimura
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C
Kubo
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H
Kanaide
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016257:Fura-2; D006490:Hemostatics / Q000494:pharmacology*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D019335:Nitroarginine / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D013552:Swine; D013917:Thrombin / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D004791:Enzyme Inhibitors; D006490:Hemostatics; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019001:Nitric Oxide Synthase; D013917:Thrombin; D002118:Calcium; D016257:Fura-2