Opening of Small and Intermediate Calcium-Activated Potassium Channels Induces Relaxation Mainly Mediated by Nitric-Oxide Release in Large Arteries and Endothelium-Derived Hyperpolarizing Factor in Small Arteries from Rat
Opening of Small and Intermediate Calcium-Activated Potassium Channels Induces Relaxation Mainly Mediated by Nitric-Oxide Release in Large Arteries and Endothelium-Derived Hyperpolarizing Factor in Small Arteries from Rat
复制标题
大鼠中小和中级钙激活钾通道的开放引起松弛，主要由大动脉中一氧化氮的释放和小动脉中内皮衍生的超极化因子介导
DOI：
--
复制
发表时间：
2011
影响因子：
3.5
通讯作者：
U. Simonsen
中科院分区：
文献类型：
--
作者：
E. Stankevičius;T. Dalsgaard;C. Krøigaard;Lilliana Beck;E. Boedtkjer;M. Misfeldt;Gorm Nielsen;Olav Schjorring;A. Hughes;U. Simonsen
本研究旨在探讨由6，7-二氯-1H-吲哚-2，3-二酮3-肟（NS 309）激活的小电导（SKCa或KCa 2）和中等电导（IKCa或KCa 3.1）钙激活钾通道是否参与大鼠肠系膜大动脉和小动脉的一氧化氮（NO）和内皮源性超极化因子（EDHF）型舒张。将大鼠上级和小肠系膜动脉的节段固定在肌电描记器中用于功能研究。使用NO微传感器记录NO。在人脐静脉内皮细胞（HUVECs）中研究SKCa和IKCa通道电流和mRNA表达，并在HUVECs和肠系膜动脉内皮细胞中研究钙浓度。在上级（直径1093 μm）和小肠系膜（直径300 μm）动脉中，NS 309均引起内皮依赖性和浓度依赖性舒张。在上级肠系膜动脉中，NS 309舒张和NO释放分别被NG、NG-不对称二甲基-l-精氨酸（ADMA）（300 μM）（一种NO合酶抑制剂）和apamin（0.5 μM）加1-[（2-氯苯基）二苯基甲基]-1H-吡唑（TRAM-34）（1 μM）（SKCa和IKCa通道阻断剂）抑制。在小肠系膜动脉，NS 309松弛略有减少ADMA，而apamin加上IKCa通道阻滞剂几乎废除放松。伊比利亚毒素不改变NS 309松弛。HUVECs表达SKCa和IKCa通道的mRNA，NS 309诱导钙、外向电流和NO释放的增加，这些增加被蜂毒肽和TRAM-34或Charybdotoxin阻断。这些结果表明，开放的SKCa和IKCa通道导致内皮依赖性舒张，主要是由NO介导的大肠系膜动脉和EDHF型舒张小肠系膜动脉。NS 309诱导的钙内流似乎有助于NO的形成。
This study was designed to investigate whether calcium-activated potassium channels of small (SKCa or KCa2) and intermediate (IKCa or KCa3.1) conductance activated by 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309) are involved in both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF)-type relaxation in large and small rat mesenteric arteries. Segments of rat superior and small mesenteric arteries were mounted in myographs for functional studies. NO was recorded using NO microsensors. SKCa and IKCa channel currents and mRNA expression were investigated in human umbilical vein endothelial cells (HUVECs), and calcium concentrations were investigated in both HUVECs and mesenteric arterial endothelial cells. In both superior (∼1093 μm) and small mesenteric (∼300 μm) arteries, NS309 evoked endothelium- and concentration-dependent relaxations. In superior mesenteric arteries, NS309 relaxations and NO release were inhibited by both NG,NG-asymmetric dimethyl-l-arginine (ADMA) (300 μM), an inhibitor of NO synthase, and apamin (0.5 μM) plus 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34) (1 μM), blockers of SKCa and IKCa channels, respectively. In small mesenteric arteries, NS309 relaxations were reduced slightly by ADMA, whereas apamin plus an IKCa channel blocker almost abolished relaxation. Iberiotoxin did not change NS309 relaxation. HUVECs expressed mRNA for SKCa and IKCa channels, and NS309 induced increases in calcium, outward current, and NO release that were blocked by apamin and TRAM-34 or charybdotoxin. These findings suggest that opening of SKCa and IKCa channels leads to endothelium-dependent relaxation that is mediated mainly by NO in large mesenteric arteries and by EDHF-type relaxation in small mesenteric arteries. NS309-induced calcium influx appears to contribute to the formation of NO.
影响因子：
7.3
作者：
Damkjaer, Mads;Nielsen, Gorm;Kohler, Ralf
通讯作者：
Kohler, Ralf