Gojkoviíc Bukarica L, Kazić T, Sajić Z, Djukanović B, Panić G, Perić M, Bojić M
Department of Pharmacology, Medical Faculty, Belgrade, Yugoslavia.
Fundam Clin Pharmacol. 1997;11(6):550-60. doi: 10.1111/j.1472-8206.1997.tb00860.x.
The present study was undertaken to examine the effects of pinacidil and levcromakalim, two potassium, channel openers, on human internal mammary artery (HIMA) obtained from patients undergoing coronary artery bypass surgery, and to clarify the contribution of different K+ channel subtypes in pinacidil and levcromakalim action in this blood vessel. Pinacidil and levcromakalim induced a concentration-dependent relaxation of the precontracted arterial segments (pEC50 = 5.77 +/- 0.05 and 6.89 +/- 0.03, respectively), 4-Aminopyridine (3 mM), a non-selective blocker of K+ channels, induced significant shifts to the right of the concentration-response curves for pinacidil and levcromakalim. Tetraethylammonium (6 mM), charybdotoxin (0.4 microM) and apamin (0.1 microM), blockers of Ca(2+)-sensitive K+ channels, had no effect on the pinacidil- and levcromakalim-evoked relaxation. Glibenclamide (0.1-10 microM), a selective blocker of adenosine triphosphate (ATP)-sensitive K+ channels, competitively antagonized the response to levcromakalim (pKB = 7.92 +/- 0.07). In contrast, glibenclamide, in significantly higher concentrations (3-30 microM), non-competitively antagonized the response to pinacidil. High concentrations of pinacidil (> 10 microM) relaxed arterial rings bathed by a medium containing 100 mM K+ with maximum response 83 +/- 6%. Under the same conditions, the maximum levcromakalim-induced relaxation on HIMA was almost abolished (15 +/- 2%). It is concluded that pinacidil and levcromakalim do not relax the HIMA through the same subtype of K+ channel. ATP-sensitive K+ channels are probably involved in levcromakalim- but not in a pinacidil-induced relaxation in the HIMA. In addition, in pinacidil-induced relaxation of the HIMA, K+ channel-independent mechanisms seem to be involved.
本研究旨在考察吡那地尔和左西孟旦这两种钾通道开放剂对取自接受冠状动脉搭桥手术患者的人乳内动脉（HIMA）的影响，并阐明不同钾通道亚型在吡那地尔和左西孟旦对该血管作用中的贡献。吡那地尔和左西孟旦可使预收缩的动脉段产生浓度依赖性舒张（pEC50分别为5.77±0.05和6.89±0.03），钾通道非选择性阻滞剂4-氨基吡啶（3 mM）可使吡那地尔和左西孟旦的浓度-反应曲线显著右移。钙敏感性钾通道阻滞剂四乙铵（6 mM）、蝎毒素（0.4 μM）和蜂毒明肽（0.1 μM）对吡那地尔和左西孟旦引起的舒张无影响。三磷酸腺苷（ATP）敏感性钾通道选择性阻滞剂格列本脲（0.1 - 10 μM）竞争性拮抗左西孟旦的反应（pKB = 7.92±0.07）。相反，格列本脲在显著更高浓度（3 - 30 μM）时非竞争性拮抗吡那地尔的反应。高浓度的吡那地尔（>10 μM）可使置于含100 mM钾的培养基中的动脉环舒张，最大反应为83±6%。在相同条件下，左西孟旦对HIMA的最大舒张作用几乎消失（15±2%）。结论是吡那地尔和左西孟旦并非通过相同亚型的钾通道使HIMA舒张。ATP敏感性钾通道可能参与左西孟旦而非吡那地尔引起的HIMA舒张。此外，在吡那地尔引起的HIMA舒张中，似乎涉及钾通道非依赖机制。
