BOLD MRI: Application to Intrarenal Oxygenation

超出提供的空间。高血压，也称为高血压，在美国每四个成年人中就有一个受到影响，是中风、心脏病发作和肾脏疾病的主要风险因素。它有时被称为“沉默的杀手”，因为它通常没有症状。由于缺乏对高血压基本病理生理学的透彻了解，在预防和治疗高血压方面的进展受到阻碍。过去十年在血管生物学方面取得的重大进展使人们能够更好地了解许多潜在的机制，这随后导致了治疗高血压的新药物的开发。许多人现在认为肾脏在高血压的病理生理学中起着重要作用。具体地说，人们认为肾髓质血流量对高血压有直接影响。肾脏的改变是高血压的原因还是后果，这仍然是一个有争议的话题。无论是哪种情况，一种非侵入性的方法探测肾脏内区域水平的血流将允许验证许多假说，并在人类身上进行测试。根据以往对肾脏的血氧水平依赖(BOLD)磁共振成像(MRI)技术的经验，我们假设该技术对髓内血流的变化很敏感。更具体地说，我们认为，该技术与适当的内皮依赖血管活性药物相结合，将允许以非侵入性方式进行肾微血管反应性研究。血管反应性研究寻找血管壁对血管活性物质或生理范式的反应，这些反应可引发内源性血管活性反应。人们认为，这些微血管水平的功能变化发生得比高血压的发展要早得多，如果足够早地发现，新的治疗方法可能会逆转这些变化。在这项提议中，我们将进行实验，在先前建立的动物模型中验证我们的假设在几种形式的高血压中的有效性，然后将其扩展到人类肾脏。动物模型将允许直接比较大胆的MRI测量和侵入性激光探针评估。我们的人体研究旨在检验这一假设，即有高血压风险的受试者将表现出肾微血管反应性降低。成功的结果将有助于更好地了解人类高血压的病理生理学。PERFORMANCESITE(========================================Section End===========================================

EXCEED THE SPACE PROVIDED. Hypertension, also known as high blood pressure, affects one in four adults in the United States, and is a major risk factor for stroke, heart attack and kidney disease. It is sometimes called the "silent killer" because it often has no symptoms. Progress towards preventing and curing hypertension has been impeded by a lack of thorough understanding of its underlying pathophysiology. Significant progress made over the last decade in vascular biology has allowed for better understanding of many of the underlying mechanisms, which then has led to development of novel drug treatments for hypertension. Many now believe that kidney plays an important role in the pathophysiology of hypertension. Specifically, it is thought that renal medullary blood flow has a direct influence on hypertension. It is still a topic of debate as to the alterations in the kidney being the cause or the consequence of hypertension. In either case, availability of a non-invasive method to probe blood flow at a regional level within the kidney would allow for verifying many of the hypotheses to be tested in humans. Based on previous experience with blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) technique to the kidney, we hypothesize that the technique would be sensitive to changes in medullary blood flow. More specifically, we believe that the technique in combination with suitable endothelium-dependent vasoactive agents would allow for renal microvascular reactivity studies to be performed in a non-invasive way. Vascular reactivity studies look for responses in the vessel walls to vasoactive substances or physiological paradigms that elicit an endogenous vasoactive response. It is believed that these functional changes at the microvascular level take place much earlier than the development of hypertension and if detected early enough, may be reversed with novel therapeutic approaches. In this proposal, we will perform experiments that will validate our hypothesis in several forms of hypertension in previously well established animal models and then extend them to human kidneys. Animal models will allow for direct comparison of BOLD MRI measurements against invasive laser probe assessments. Our human studies are designed to test the hypothesis that subjects at risk for developing hypertension will exhibit reduced renal microvascular reactivity. Successful outcome will provide better understanding of pathophysiology of human hypertension. PERFORMANCESITE( ========================================Section End===========================================