Roles of cyclic AMP and Ca2+-activated K+ channels in endothelium-independent relaxation by urocortin in the rat coronary artery
Roles of cyclic AMP and Ca2+-activated K+ channels in endothelium-independent relaxation by urocortin in the rat coronary artery
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DOI：
10.1016/s0008-6363(02)00773-3
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发表时间：
2003-03-01
影响因子：
10.8
通讯作者：
Yao, XQ
中科院分区：
文献类型：
--
作者：
Huang, Y;Chan, FL;Yao, XQ
目的：尿皮质素（Urocortin）对心肌缺血再灌注损伤具有保护作用。我们的前期研究表明，Urocortin可诱导内皮依赖性和非依赖性冠脉舒张。然而，尿皮质素触发内皮非依赖性舒张的机制尚未研究。本研究旨在探讨环磷酸腺苷和钙激活的钾通道在尿皮质素舒张内皮剥脱大鼠冠状动脉左前降支中的作用。方法：采用多功能肌电描记系统中的力传感器测量血管张力的变化。结果如下：在9，11-双脱氧-11 α，9 α-环氧-甲酰基前列腺素F-2 α（U46619）收缩环中，环AMP依赖性蛋白激酶（PKA）抑制剂Rp-cAMPS三乙胺（Rp-cAMPS）和KT 5720显著降低了尿皮质素诱导的舒张（pD（2）：8.40+/-0.04）。用大电导Ca 2+激活的K+通道阻断剂、伊比利亚毒素或四乙基铵离子（TEA（+））处理可减弱尿皮质素诱导的舒张：在200 nmol/l KT 5720存在下，这种作用被消除。相反。apamin（小电导Ca 2+激活的K+通道阻滞剂）、格列本脲（ATP敏感性K+通道阻滞剂）或BaCl 2（内向整流性K+通道阻滞剂）无影响。随着细胞外K'浓度的增加（35和50 mmol/l），尿皮质素诱导的舒张在收缩的环中减少。TEA（+）或Rp-cAMPS可抑制urocortin的舒张作用。TEA（+）和Rp-cAMPS联合治疗没有额外的效果。同样，毛喉素产生显着更少的舒张反应，在50毫摩尔/升K收缩比U46619收缩环。用3 mmol/l TEA 4预处理可减弱毛喉素诱导的舒张。结论：尿皮质素通过激活血管Ca 2+激活的K+通道使大鼠冠状动脉舒张，这种作用似乎主要通过PKA依赖性细胞内机制介导。(C)2003年欧洲心脏病学会。由Elsevier Science B. V.出版，版权所有。
Objective: Urocortin possesses cardioprotectivc properties against the damaging effects of ischemia/reperfusion injury. Our previous study demonstrated that Urocortin can induce both endothelium-dependent and -independent coronary relaxation. However, the mechanisms thereby urocortin triggers endothelium-independent relaxation have not been investigated. The present study aimed to examine the role of cyclic AMP and Ca2+-activated K+ channels in the relaxant response to urocortin in the isolated endothelium-denuded rat left anterior descending coronary arteries. Methods: Changes in vessel tension were measured by Using a force transducer built in a Multi Myograph System. Results: In 9,11-dideoxy-11alpha,9alpha-epoxy-methanoprostaglandin F-2alpha (U46619)-contracted rings, urocortin-induced relaxation (pD(2): 8.40+/-0.04) was significantly reduced by cyclic AMP-dependent protein kinase (PKA) inhibitors, Rp-cAMPS triethylamine (Rp-cAMPS) and KT 5720. Treatment with the large-conductance Ca2+-activated K+ channel blockers, iberiotoxin or tetraethylammonium ions (TEA(+)) attenuated urocortin-induced relaxation: this effect was abolished in the presence of 200 nmol/l KT 5720. In contrast. apamin (small-conductance Ca2+-activated K+ channel blocker), glibenclamide (ATP-sensitive K+ channel blocker), or BaCl2 (inwardly rectifier K+ channel blocker) had no effect. Urocortin-induced relaxation was reduced in rings contracted with increasing concentrations of extracellular K' (35 and 50 mmol/l). Treatment with TEA(+) or Rp-cAMPS inhibited the relaxant effect of urocortin in 35 mmol/L K+-contracted rings. Combined treatment with TEA(+) and Rp-cAMPS had no additional effect. Similarly, forskolin produced significantly less relaxant response in 50 Mmol/l K -contracted than U46619-contracted rings. Forskolin-induced relaxation was attenuated by pretreatment with 3 mmol/l TEA 4. Conclusion: Urocortin relaxed the rat coronary artery in substantial part via activation of the vascular Ca2+-activated K+ channels and this effect appears to be primarily Mediated through PKA-dependent intracellular mechanisms. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.