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

研究1.人冠状小动脉血流依赖性血管舒张的机制解剖人冠状小动脉并插管。在可变流量下，用视频显微镜检查其内径变化。然后，我们测试了在有和没有NO合成抑制的情况下对流动的响应，NG-单甲基-L-精氨酸（L-NMMA）。NO合成的抑制可显著减弱血流依赖性血管舒张，Gi和KATP通道的抑制可部分减弱血管舒张。内皮源性NO依赖性机制在人冠状动脉微血管的流量依赖性血管舒张中起重要作用。此外，内皮源性超极化因子（EDHF）参与FTD，L-NMMA和INDO不能完全阻断FTD。鲎毒素加蜂毒肽或四丁基铵可显著降低FID。因此，EDHF介导的人冠状动脉扩张是由K^+通道（包括Kca通道）介导的。增强的可靠性 关于我们 充血性心力衰竭（CHF）大鼠小冠状动脉内皮源性超极化因子（EDHF）的变化，本研究的目的是确定CHF大鼠小冠状动脉血流诱导性舒张（FID）是否发生改变，以及EDHF在这一过程中的作用。从对照大鼠和通过左冠状动脉结扎诱导的CHF大鼠中分离小冠状动脉，并在流动下插管。两组间FED无显著差异。L-NMMA对对照组大鼠血管FID的抑制作用大于CHF组。吲哚美辛（INDO）预处理对FID的影响最小。与对照大鼠相比，在L-NMMA和INDO存在下，KCl在CHF大鼠血管中的FID衰减程度更大。通过去除内皮来消除FID。与对照大鼠血管相比，在接受了蜂毒毒素和蜂毒肽或四丁基铵后，CHF大鼠血管中的FID显著降低，而17-十八炔酸对对照和CHF大鼠血管中的FID影响很小。小冠状动脉的FID由K^+通道（包括Kca通道）介导。EDHF介导的舒张功能可弥补CHF时NO介导的舒张功能的丧失。少

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