IS SMOOTH MUSCLE DYSFUNCTION AN EARLY EVENT IN ATHEROSCLEROSIS?

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。“固定流量”的概念已经被人熟知了几十年。报告指出，服用硝酸甘油后，冠心病患者的冠脉血流量和氧耗量没有变化。这是因为缺血是一种强大的刺激，血管的大部分扩张能力被用来维持静止的血液流动。此外，最近的研究表明，与健康对照组相比，冠心病患者管道血管对一氧化氮供体硝酸甘油的扩张剂反应减弱。其他研究表明，在动脉粥样硬化中，只有内皮依赖性的扩张受到损害。我们打算比较健康受试者、吸烟者和动脉粥样硬化患者的血管内皮依赖性扩张和非内皮依赖性血管扩张。到目前为止，还没有研究同时使用外源性一氧化氮供体扩张器(如硝酸甘油)和非一氧化氮介导的扩张器(如硝苯地平)来测试管道血管的功能。这将使用户能够区分功能障碍是在血管壁的平滑肌层(中膜)还是由于一氧化氮失活。我们假设动脉粥样硬化会导致主要的血管平滑肌功能障碍。作为第二个目标，我们计划比较β2激动剂(如沙丁胺醇)作为血管内皮依赖性扩张剂和内皮依赖性血流介导的扩张剂的血管扩张作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The "fixed flow" concept is one that has been known for several decades. It states that following nitroglycerin, coronary blood flow and oxygen consumption were unchanged in patients with coronary artery disease. This is because ischemia is a powerful stimulus and much of the capacity of the vessel to dilate is utilized to maintain resting blood flow. Additionally, recent studies showed that the vasodilator response of conduit vessels to a nitric oxide donor nitroglycerin is impaired in subjects with coronary artery disease when compared to healthy controls. Other studies have suggested that only endothelium-dependent dilatation is impaired in atherosclerosis. We intend to compare endothelium-dependent and independent dilatation of conduit vessels in healthy subjects, smokers, and atherosclerotic patients. To date, no study has tested conduit vessel function using both an exogenous nitric oxide-donor dilator (such as nitroglycerin) and a non-nitric oxide mediated dilator (such as nifedipine). This will enable use to differentiate whether the dysfunction is in the smooth muscle (tunica media) layer of the vessel wall or due to nitric oxide inactivation. We hypothesize that atherosclerosis causes a predominant vascular smooth muscle dysfunction. As a secondary aim, we plan to investigate the vasodilator effect of beta 2-agonists (such as albuterol) as endothelium dependent dilators of conduit vessels in comparison with endothelium dependent flow-mediated dilatation.