Azzawi May, Austin Clare
Smooth Muscle Physiology Group, Division of Cardiovascular and Endocrine Sciences, Core Technology Facility, University of Manchester, Manchester, UK.
J Vasc Res. 2007;44(3):223-33. doi: 10.1159/000100421. Epub 2007 Feb 28.
The aims of this study were to investigate, for the first time, the effects of endothelial factor inhibition on both the magnitude and dynamics of the response of isolated small coronary arteries to intraluminal flow. Isolated rat coronary arteries were mounted on a pressure myograph and left to develop myogenic tone. Flow was introduced and maintained until stable diameters were attained. Dilatory responses were observed which were maximal at low flow rates (5-10 microl/min) and thus shear stresses (1-2 dyn/cm(2)). These responses were transient in nature. Transient dilations were also observed upon cessation of flow. All responses (to 5 microl/min) were endothelium dependent and were completely abolished by addition of charybdotoxin (100 nM) and apamin (100-500 nM) suggesting an important role for a hyperpolarizing mechanism most likely involving an endothelium-derived hyperpolarizing factor. However, inhibitors of nitric oxide synthase (L-NNA; 100 microM) or cyclo-oxygenase (indomethacin; 10 microM) also modulated the response causing an increase and decrease in maximum vasodilation, respectively. By examining the time course we showed that both agents also made the response significantly more transient in nature. These results show that inhibition of endothelial factor pathways can influence both the magnitude and dynamics of the response of isolated rat coronary arteries to flow.
本研究的目的是首次探究内皮因子抑制对离体小冠状动脉对腔内血流反应的幅度和动力学的影响。将离体大鼠冠状动脉安装在压力肌动描记仪上，使其产生肌源性张力。引入并维持血流直至达到稳定直径。观察到扩张反应，在低流速（5 - 10微升/分钟）以及由此产生的剪切应力（1 - 2达因/平方厘米）时最大。这些反应本质上是短暂的。在血流停止时也观察到短暂扩张。所有对5微升/分钟的反应均依赖于内皮，加入蝎毒素（100纳摩尔）和蜂毒明肽（100 - 500纳摩尔）后反应完全消失，这表明一种超极化机制发挥了重要作用，极有可能涉及一种内皮源性超极化因子。然而，一氧化氮合酶抑制剂（L - NNA；100微摩尔）或环氧化酶抑制剂（吲哚美辛；10微摩尔）也调节了反应，分别导致最大血管舒张增加和减少。通过检查时间进程，我们发现这两种药物还使反应在本质上显著更短暂。这些结果表明，抑制内皮因子途径可影响离体大鼠冠状动脉对血流反应的幅度和动力学。
