The Effects of Potassium Channel Opener P1075 on the Human Saphenous Vein and Human Internal Mammary Artery
The Effects of Potassium Channel Opener P1075 on the Human Saphenous Vein and Human Internal Mammary Artery
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DOI：
10.1097/fjc.0b013e3182145850
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发表时间：
2011-06
影响因子：
3
通讯作者：
L. Gojković-Bukarica;B. Beleslin-Čokić;A. Novaković;M. Perić;J. Marković-Lipkovski;S. Ćirović;D. Nežić;A. Lešić;V. Kanjuh;H. Heinle
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文献类型：
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作者：
L. Gojković-Bukarica;B. Beleslin-Čokić;A. Novaković;M. Perić;J. Marković-Lipkovski;S. Ćirović;D. Nežić;A. Lešić;V. Kanjuh;H. Heinle
由于肾上腺素能收缩可导致冠状动脉旁路移植术后危及生命的痉挛，本研究旨在观察腺苷3-磷酸（ATP）敏感性钾通道（KATP）开放剂P1075对离体人隐静脉（HSV）和人乳内动脉（HIMA）收缩的影响。通过电场刺激（20 Hz）和去甲肾上腺素诱发相性收缩。持续性收缩由苯肾上腺素诱发。免疫形态学证实了HIMA中KATP通道的成孔Kir6.1和Kir6.2亚基的存在以及HSV中仅Kir6.2亚基的存在。P1075仅对HSV有抑制作用，电场刺激收缩作用强于去甲肾上腺素收缩作用。此外，HSV的苯肾上腺素收缩对P1075比HIMA更敏感。KATP通道阻断剂格列本脲对P1075引起的两种移植血管舒张作用的拮抗作用不同，因为格列本脲对P1075引起的HSV收缩的抑制作用比对HIMA的抑制作用更显著。我们的结论是，P1075具有血管舒张作用，抑制肾上腺素能收缩的测试移植。这种效应是移植物和血管收缩剂选择性的，似乎是由Kir6.1和/或Kir6.2含有KATP通道介导的。因此，P1075可以被认为是一种潜在的预防移植物痉挛的药物。
Because adrenergic contractions can contribute to the development of life-threatening spasm of coronary artery bypass graft, this study was performed to investigate the effect of adenosine 3-phosphate (ATP)-sensitive K+ channel (KATP) opener P1075 on contractions of isolated human saphenous vein (HSV) and human internal mammary artery (HIMA). Phasic contractions were evoked by electric field stimulation (20 Hz) and noradrenaline. The sustained contractions were evoked by phenylephrine. The presence of pore-forming Kir6.1 and Kir6.2 subunits of the KATP channels in the HIMA and only Kir6.2 in the HSV was confirmed immunomorphologically. P1075 inhibited in the HSV only, the electrical field stimulation contractions more strongly than noradrenaline contractions. In addition, the phenylephrine contractions of HSV were more sensitive to P1075 in comparison to those of HIMA. Glibenclamide, a KATP channel blocker antagonized the vasodilatation produced by P1075 in both grafts differently, because its effect was more prominent on the P1075-induced inhibition of contractions of HSV than of HIMA. We conclude that P1075 has a vasorelaxant effect and inhibited adrenergic contractions of the tested grafts. This effect is graft and vasoconstrictor selective and seems to be mediated by Kir6.1- and/or Kir6.2-containing KATP channels. Thus, P1075 can be considered as a potential drug in the prevention of graft spasm.