IS SMOOTH MUSCLE DYSFUNCTION AN EARLY EVENT IN ATHEROSCLEROSIS?

平滑肌功能障碍是动脉粥样硬化的早期事件吗？

• 批准号: 7377011
• 负责人: WILLIAM G HAYNES
• 金额: $ 0.53万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377011
• 关键词: SMOOTH; MUSCLE; DYSFUNCTION; EARLY; EVENT

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。“固定流量”概念是一个已经知道了几十年的概念。它指出，服用硝酸甘油后，冠状动脉疾病患者的冠状动脉血流量和耗氧量没有变化。这是因为缺血是一种强有力的刺激，血管扩张的大部分能力被用来维持静息血流。此外，最近的研究表明，与健康对照组相比，冠状动脉疾病受试者的导管血管对一氧化氮供体硝酸甘油的血管扩张反应受损。其他研究表明，动脉粥样硬化中只有内皮依赖性扩张受损。 我们打算比较健康受试者、吸烟者和动脉粥样硬化患者的导管血管内皮依赖性和独立性扩张。到目前为止，还没有研究使用外源性一氧化氮供体扩张剂（如硝酸甘油）和非一氧化氮介导的扩张剂（如硝苯地平）测试管道血管功能。这将能够用于区分功能障碍是在血管壁的平滑肌（图尼卡中膜）层中还是由于一氧化氮失活。我们推测动脉粥样硬化导致主要的血管平滑肌功能障碍。作为次要目的，我们计划研究β 2受体激动剂（如沙丁胺醇）作为导管血管内皮依赖性扩张剂的血管扩张作用，并与内皮依赖性血流介导的扩张作用进行比较。