过刊浏览

Idoxifene对人乳内动脉的舒张作用

韦耿泽, 于军, 朱运龙, 林树新, 康云帆, 王嵘, 周京军, 张庆红

第四军医大学生理学教研室.陕西,西安 710032；第四军医大学病理生理学教研室.陕西,西安 710032；第四军医大学西京医院心血管外科中心.陕西,西安 710032；第四军医大学外语教研室.陕西,西安 710032

摘要

为了研究idoxifene(吲哚昔酚,一种新型雌激素受体调节剂)对人乳内动脉(HIMA)的舒张作用及其机制,采用离体血管灌流的方法,观察idoxifene对完整内皮和去内皮HIMA的舒张作用,以及L--NAME和美蓝(MB)对这一过程的影响,并且和17#beta#雌二醇(17#beta#--estradiol,E_(2))的舒血管作用进行了比较。实验中观察到保留血管内皮时idoxifene(0.01--10#mu#mol/L)和E_(2)(0.1--100#mu#mol/L)可以剂量依赖性地舒张血管,且血管对idoxifene的灵敏度比对E_(2)高15倍左右,而去内皮时则无此作用;NO合成酶阻断剂L--NAME和鸟苷酸环化酶(GC)的抑制剂MB使idoxifene舒张HIMA的作用完全消失。上述结果表明:idoxifene能够剂量依赖性地舒张HIMA,而且比E_(2)更有效。idoxifene的这种作用是通过NO--GC--cGMP通路实现的。

关键词： 吲哚昔酚(idoxifene); 雌激素; 人乳内动脉; 血管舒张

Vasorelaxing effect of idoxifene on human internal mammary arteries

Wei Gengze, Yu Jun, Zhu Yunlong, Lin Shuxin, Kang Yunfan, Wang Rong, Zhou Jingjun, Zhang Qinghong

Department of Physiology,Fourth Military Medical University.Xi^an 710032,Shaanxi；China；Cardiovascular Surgery Center of Xijing Hospital,Fourth Military Medical University.Xi^an 710032,Shaanxi

Abstract

The results obtained from idoxifene were compared with those from 17#beta#-estradil (E_(2)). It was found that idoxifene caused a concentration-dependent relaxation of HIMA. The dose range was from 0.03 #mu#mol/L (minimal vasodilatory concentration) to 3 mmol/L (maximal vasodilatory concentration). It was also found that the vasorelaxation effect of idoxifene on HIMA was dependent on endothelium. E_(2) (0.1--100 #mu#mol/L) also resulted in an endothelium,-dependent vasorlaxation, but the vessels were 15-fold less sensitive to E_(2) than to idoxifene in their vasorelaxation responses. The EC_(50) for E_(2) was 4.65±0.34 #mu#mol/L, compared with 0.32±0.02 #mu#mol/L for idoxifene. The mean maximal vasodilatory value of E_(2) was 88.3±5.7%, compared with 88.6±7.2% for idoxifene. Pretreatment withi L-NAME (100 #mu#mol/L) abolished idoxifene-induced vasodilation virtually by blocking nitric oxide production. The vasorelaxing effect of idoxifene disappeared in the presnece of MB (10 #mu#mol/L). These findings demonstrate that idoxifene results in an endothelium-dependent vasorelaxation of HIMA, like estrogen. The effect of idoxifene is more potent than that of traditional estrogen, and is possibly mediated by NO-GC-cGMP pathway.

Key words: idoxifene;Estrogen;human internal mammary artery;Vasodilation

收稿日期：　　录用日期：

通讯作者：　　E-mail:

引用本文：

韦耿泽, 于军, 朱运龙, 林树新, 康云帆, 王嵘, 周京军, 张庆红. Idoxifene对人乳内动脉的舒张作用[J]. 生理学报 2004; 56 (1): .

Wei Gengze, Yu Jun, Zhu Yunlong, Lin Shuxin, Kang Yunfan, Wang Rong, Zhou Jingjun, Zhang Qinghong. Vasorelaxing effect of idoxifene on human internal mammary arteries. Acta Physiol Sin 2004; 56 (1): (in Chinese with English abstract).