IS SMOOTH MUSCLE DYSFUNCTION AN EARLY EVENT IN ATHEROSCLEROSIS?

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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.