Division of Clinical Physiology, Institute of Cardiology, Medical and Health Science Center, University of Debrecen, Móricz Zs. krt. 22, H-4032 Debrecen, Hungary.
Pharmacol Rep. 2013;65(5):1304-10. doi: 10.1016/s1734-1140(13)71488-9.
Levosimendan and its long-lived metabolite OR-1896 produce vasodilation in different types of vessels by activating ATP-sensitive (KATP) and other potassium channels.
In the present study we applied intravital videomicroscopy to investigate the in situ effects of levosimendan and OR-1896 on the diameters of real resistance arterioles (rat cremaster muscle arterioles with diameters of ≈ 20 μm).
Levosimendan and OR-1896 induced concentration-dependent (1 nM - 100 μM) dilations to similar extents in these arterioles (maximal dilation from 23 ± 2 to 33 ± 2 μm and from 22 ± 1 to 32 ± 1 μm, respectively). The arteriolar dilations induced by the selective KATP channel opener pinacidil (1 nM - 10 μM) (maximal dilation from 22 ± 4 μm to 35 ± 3 μm) were diminished in the presence of the selective KATP channel blocker - glibenclamide (5 μM) (maximal diameter attained: 22 ± 1 μm). Glibenclamide also counteracted the maximal dilations in response to levosimendan or OR-1896 (to 23 ± 3 μm or 22 ± 5 μm, respectively).
In conclusion, this is the first demonstration that levosimendan and OR-1896 elicit arteriolar dilation in vivo, via activation of KATP channels in real resistance vessels in the rat.
左西孟旦及其长半衰期代谢产物 OR-1896 通过激活三磷酸腺苷敏感 (KATP) 和其他钾通道，在不同类型的血管中产生血管扩张作用。
在本研究中，我们应用活体视频显微镜技术，研究了左西孟旦和 OR-1896 对真实阻力小动脉（大鼠提睾肌小动脉，直径约 20μm）直径的原位作用。
左西孟旦和 OR-1896 在这些小动脉中诱导浓度依赖性（1 nM-100 μM）扩张，程度相似（最大扩张分别为 23±2μm 和 22±1μm 至 33±2μm 和 32±1μm）。选择性 KATP 通道 opener 吡那地尔（1 nM-10 μM）引起的小动脉扩张（最大扩张从 22±4μm 到 35±3μm）在选择性 KATP 通道阻滞剂 - 格列本脲（5μM）存在时被减弱（最大直径达到：22±1μm）。格列本脲还拮抗了左西孟旦或 OR-1896 引起的最大扩张（分别为 23±3μm 或 22±5μm）。
总之，这是首次证明左西孟旦和 OR-1896 通过激活大鼠真实阻力血管中的 KATP 通道，在体内引起小动脉扩张。
