The role of endothelium-derived hyperpolizing factor in shear stress in coronary resistance vessels

内皮源性过度化因子在冠状动脉阻力血管剪切应力中的作用

• 批准号: 13670764
• 负责人: OHYANAGI Mitsumasa
• 金额: $ 0.38万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670764/
• 关键词: endothelium-derived hyperpolarizing factor; coronary arteriole; Flow-induced dilation; heset failure; microcirculation; corony artery; shear stress; microcirculation

Study 1. The mechanism of flow-dependent vasodilation of human small coronay arteries.Human coronary arterioles were dissected and cannulated. At variable flow, changes in their internal diameter were examined with videomicroscopy. We then tested the response to flow with and without inhibition of NO syntheses, NG-Monomethy-L-atginine (L-NMMA). Flow-dependent vasodilation was significantly attenuated by inhibition of NO syntheses, and vasodilation was partially attenuated with inhibition of Gi and KATP channels. Endothelial-derived NO-dependent mechanisms play an important role in flow-dependent vasodilation in human coronaty microvessels. Moreover, endothelium-derived hyperpolarizing factor (EDHF) was involved in FTD that was not blocked completely by L-NMMA and INDO. FID was significantly decreased by charybdotoxin plus apamin or tetrabutylamnmonium. Therefore, EDHF-mediated dilation of human coronary arterioles is mediated by K^+ channels including Kca channels.Study 2. Enhanced rel … More ease of endothelium-derived hyperpolarizing factor in small coronary arteries from rats with congestive heart failure (CHF).The aim of this study was to determine whether flow-induced dilation (FID) is altered in small coronary arteries from CHF rats and to characterize the role of EDHF in this process. The small coronary arteries were isolated from control rats and from rats with CHF induced by left coronary artery ligation and were cannulated with flow. There was no significant difference in FED between the two groups. FID in control rat vessels showed greater attenuated by L-NMMA than vessels from CHF rats. Pretreatment with indomethacin (INDO) only minimally affected FID. FID was attenuated to a greater degree in CHF rat vessels by KCl in the presence of L-NMMA and INDO compared to control rat. FID was abolished by removal of the endothelium. FID was significantly decreased in vessels from CHF rats in response to charybdotoxin plus apamin or tetrabutylamnmomium when compared to control rat vessels, while 17-octadecynoic acid had only minimal affect on FID in both control and CHF rat vessels FID of small coronary arteries is mediated by K^+ channels, including Kca channels. EDHF-mediated dilation may compensate for the loss of NO-mediated dilation in CHF. Less

研究1.人冠状动脉小动脉血流依赖性血管扩张的机制：解剖和插管人冠状动脉。在可变流量下，用视频显微镜观察其内径的变化。然后，我们测试了在没有和没有抑制合成NG-单甲基-L-精氨酸(L-NMMA)的情况下对Flow的反应。抑制NO的合成可显著减弱血流依赖性的血管扩张，抑制GI和KATP通道可部分减弱血管扩张。内皮来源的NO依赖机制在人类冠状微血管的血流依赖性血管扩张中起重要作用。此外，内皮衍生超极化因子参与了FTD的发生，但这一作用不能被L-NMMA和INDO完全阻断。河豚毒素联合阿帕明或四丁基铵可显著降低FID。因此，EDHF介导的人冠状动脉小动脉的扩张是由包括Kca通道在内的K~+通道介导的。研究2.增强的Rel…充血性心力衰竭(CHF)大鼠冠状动脉小血管内皮源性超极化因子的易感性。本研究的目的是确定充血性心力衰竭(CHF)大鼠冠状动脉小血管血流诱导的扩张(FID)是否发生改变，并探讨EDHF在这一过程中的作用。分离正常大鼠和左冠状动脉结扎所致心力衰竭大鼠的冠状动脉小动脉，用血流管插管。FED两组间差异无统计学意义。与CHF大鼠相比，L-NMMA对对照组大鼠血管FID的抑制作用更强。吲哚美辛(INDO)对FID的影响很小。与对照组相比，在L-NMMA和INDO存在下，氯化钾对CHF大鼠血管FID有更大程度的抑制作用。通过去除内皮来消除FID。与对照组大鼠血管相比，CHF大鼠血管内皮细胞FID明显减少，而17-十八烷酸对对照组和CHF大鼠血管FID的影响很小。小冠状动脉的FID是由K~(++)通道，包括KCA通道介导的。EDHF介导的血管扩张可补偿CHF时NO介导的血管扩张功能的丧失。较少