Vasorelaxant effect of 7-[2-(4-morpholinyl)ethoxy]chroman hydrochloride(HEF-04) and possible mechanisms  

7-[2-(4-吗啉基)乙氧基]色满盐酸的血管舒张作用及其可能的机制研究(英文)

作　　者：王冰[1] 付守廷[1] 胡春[2] 朱岚[1] 韦元元[1] 

机构地区：[1]沈阳药科大学生命科学院与生物制药学院,辽宁沈阳110016 [2]沈阳药科大学生物工程与生物制药学院,辽宁沈阳110016

出　　处：《Journal of Chinese Pharmaceutical Sciences》2010年第2期115-119,共5页中国药学（英文版）

摘　　要：This study aimed to investigate the relaxant effect of chroman compound HEF-04 on isolated vascular smooth muscle （VSM） and the possible underlying mechanisms involved. Isolated rabbit thoracic aorta was used as the in vitro model and the relaxant effects of HEF-04 on endothelium-intact （＋EC） and endothelium-denuded （EC） thoracic aortic rings were compared. Potassium channel blockers, guanylate cyclase inhibitors, and COX-inhibitors were used to explore associations between the relaxant effects of HEF-04 with potassium channels, NO, and prostaglandin-like substances and endothelial hyperpolafizing factor （EDHF）, respectively. The results indicated that HEF-04 （1 × 10^-5 mol/L to 3× 10^-3 mol/L） had no significant impact on basal vascular tension, but could relax the contraction of vascular smooth muscle caused by high-K＋ solution in a dose-dependent manner. Indomethacin （5.6× 10^-6 mol/L） had no effect on vasorelaxation effect of HEF-04. In contrast, the vasorelaxant effect of HEF-04 was enhanced by methylene blue, which was significantly inhibited by calcium-dependent potassium channel blocker TEA. The vasorelaxant effect of HEF-04 on ＋EC thoracic aortic rings was significantly stronger than that on -EC thoracic aortic rings. The endothelium dependent relaxant effect of HEF-04 on VSM might be attributed to the interaction of HEF-04 with vascular relaxing factors or the increased release of EDHF.本文研究了色满类化合物HEF-04对离体血管平滑肌的舒张作用及其初步机制,采用离体实验的方法研究HEF-04的舒张作用,并观察比较了其对内皮完整组及去内皮组的作用的不同,分别应用钾通道阻断剂、鸟苷酸环化酶抑制剂、环合酶抑制剂来初步探讨HEF-04的作用与钾通道、NO、前列腺素类物质以及血管内皮超级化因子的关系。HEF-04(1×10^(-5)mol/L-3×10^(-3)mol/L)对血管基础张力无明显影响,却能舒张致痉剂高钾引起的收缩,并具有剂量依赖性。吲哚美辛(5.6×10^(-6)mol/L)不影响HEF-04对血管的舒张作用,与亚甲基蓝孵育前相比,亚甲基蓝没有抑制HEF-04的血管舒张作用,却使之作用增强,但这种增强作用却能被钙依赖性钾通道阻断剂TEA显著性抑制,HEF-04对内皮完整组血管舒张作用明显强于去内皮组,HEF-04具有内皮依赖性的血管舒张作用可能与血管舒张因子之间的相互作用有关,也可能由于EDHF的释放增加所致。

关 键 词：7-[2-（4-Morpholinyl） ethoxy]chroman hydrochloride VASORELAXATION EDHF 

分 类 号：R96[医药卫生—药理学]