摘要
目的 研究内皮依赖性超极化因子(EDHF)在剪切应力引起的内皮依赖性舒张反应中的作用及机制。方法 测定不同流量下的血管内径及各种内皮依赖性舒张因子抑制剂、钾通道抑制剂、细胞色素P450单氧化酶抑制剂作用下的血管内径。结果 剪切应力在大鼠肠系膜微动脉引起的舒张反应是内皮依赖性的,且在大的肠系膜动脉明显大于小阻力型肠系膜动脉。EDHF在上述两种动脉的内皮依赖性舒张反应中作用均明显大于NO,起主要作用。剪切应力引起的内皮依赖性舒张反应不受SKF525A的抑制,ChTx加apamin明显抑制了此舒张反应,TBA则几乎完全抑制此舒张反应。结论 在剪切应力引起的内皮依赖性舒张反应中EDHF起主要作用,钾通道特别是KCa通道的激活为主要机制。
Aim To investigate the role and mechanism of endothelium-derived hyperpolarizing factor (EDHF) in shear stress induced vasorelaxation of rat mesenteric artery. Methods The changes in vessel diameter in response to variable flow (0-300 μL·min^-1) were continuously examined. The contribution of prostacyclin (PGI ~2), NO and EDHF to shear stress induced relaxation were analyzed by inhibitory effects of indomethacin, N^G-nitro-L-arginine (L-NA) and KCl. The nature and hyperpolarizing mechanism of EDHF were examined by the inhibitory effects of inhibitors of cytochrome P450 pathway and of various K^+ channels. Results The shear stress-induced relaxation were endothelium dependent and the contribution of NO was more prominent in large mesenteric arteries (400-500 μm) than that in resistance arteries (150-250 μm), whereas that of EDHF was noted in both-sized blood vessels. Tetrabutylammonium (a nonselective inhibitor of K channels) almost abolished, whereas the combination of charybdotoxin (an inhibitor of both large and intermediate-conductance Ca^2+-activated K channels) and apamin (an inhibitor of small-conductance Ca^2+-activated K channels) significantly inhibited the EDHF-mediated component of the shear stress-induced relaxations. Conclusion EDHF plays an important role in shear stress-induced endothelium-dependent relaxations, and K channels especially calcium-activated K channels appear to be involved.
出处
《药学学报》
CAS
CSCD
北大核心
2005年第6期491-495,共5页
Acta Pharmaceutica Sinica
基金
教育部留学回国人员科研启动基金资助项目 ( 2001年).
关键词
剪切应力
内皮依赖性舒张反应
内皮依赖性超极化因子
钾通道
shear stress
endothelium-dependent relaxation
endothelium-derived hyperpolarizing factor
potassium channel
