中国药理学通报Issue(4)：473-477,5.DOI:10.3969/j.issn.1001-1978.2014.04.008
Rho激酶抑制剂DL0805-0对大鼠离体胸主动脉的舒张作用及机制研究
Vasorelaxant effect of Rho kinase inhibitor DL0805-0 on isolated rat aortic rings and its underlying mechanisms
摘要
Abstract
Aim To investigate the in vitro vasorelax-ant effect of DL0805-0, a Rho kinase inhibitor, on iso-lated rat thoracic aorta and explore its underlying mechanism. Methods Tension was measured to eval-uate the vasorelaxant effect of DL0805-0 on rat endo-thelium-intact and endothelium-denuded thoracic aorta rings. Rho kinase inhibitor fasudil, nitric oxide syn-thase inhibitor Nω-nitro-L-arginine methyl ester ( L-NAME), guanylate cyclase inhibitor methylene blue, cyclooxygenase inhibitor indomethacin, calcium-activa-ted potassium channel blocker tetraethyl ammonium ( TEA ) , ATP-sensitive potassium channel blocker glibenclamide and voltage-dependent potassium chan-nel blocker 4-aminopyridine ( 4-AP ) were used to il-lustrate the mechanisms of vasorelaxant effect of DL0805-0 . Results DL0805-0 exerted vasorelaxation in a dose-dependent manner in KCl (60 mmol·L-1 ) or NE ( 0. 1 μmol · L-1 ) -induced contraction. DL0805-0-induced vasorelaxation was significantly re-duced by L-NAME. However, methylene blue and in-domethacin did not significantly affect vasorelaxation of DL0805-0. In endothelium-denuded rings, TEA re-markably attenuated the vasorelaxant effect of DL0805-0 , while glibenclamide and 4-AP did not affect vasore laxation of DL0805-0 significantly. DL0805-0 also re-duced NE-induced transient contraction and inhibited contraction induced by increasing extracellular calci-um. Conclusion These results suggest that DL0805-0 induces vasorelaxation through an endothelium-depend-ent pathway. The opening of calcium-activated K+channels and blocking of Ca2+ channels in vascular smooth muscle cells may be one of the mechanisms of DL0805-0-induced vasorelaxation.关键词
Rho 激酶/DL0805-0/大鼠胸主动脉环/内皮/钾通道/钙通道Key words
Rho-kinase/DL0805-0/rat thoracic aor-tic rings/endothelium/K+ channels/Ca2+ channels分类
医药卫生引用本文复制引用
阎雨,王夙博,袁天翊,焦晓臻,谢平,方莲花,杜冠华..Rho激酶抑制剂DL0805-0对大鼠离体胸主动脉的舒张作用及机制研究[J].中国药理学通报,2014,(4):473-477,5.基金项目
国家科技部“重大新药创制”科技重大专项( No 2013ZX09103-001-008,2012ZX09103-101-078) （ No 2013ZX09103-001-008,2012ZX09103-101-078）
国际科技合作专项项目(No 2011DFR31240) （No 2011DFR31240）
