BOLD MRI: Application to Intrarenal Oxygenation

描述（由申请人提供）： 高血压，也被称为高血压，影响美国四分之一的成年人，是中风，心脏病发作和肾脏疾病的主要危险因素。它有时被称为“沉默的杀手”，因为它通常没有症状。由于对高血压的病理生理学缺乏深入的了解，高血压的预防和治疗进展一直受到阻碍。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理解许多潜在的机制，从而导致开发新的高血压药物治疗。现在许多人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，认为肾髓质血流对高血压有直接影响。它仍然是一个争论的话题，在肾脏的变化是高血压的原因或后果。在任何一种情况下，在肾脏内区域水平探测血流的非侵入性方法的可用性将允许验证许多待在人体中测试的假设。根据先前的经验，血氧水平依赖（BOLD）磁共振成像（MRI）技术的肾脏，我们假设该技术将是敏感的髓质血流的变化。更具体地说，我们认为，该技术与适当的内皮依赖性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的反应或引起内源性血管活性反应的生理学范例。据信，微血管水平的这些功能变化发生得比高血压的发展早得多，如果检测得足够早，可以用新的治疗方法逆转。在这个提议中，我们将在先前建立的动物模型中进行实验，以验证我们在几种高血压形式中的假设，然后将其扩展到人类肾脏。动物模型将允许直接比较BOLD MRI测量与侵入性激光探针评估。我们的人体研究旨在检验以下假设：有高血压风险的受试者将表现出肾微血管反应性降低。成功的结果将提供更好地了解人类高血压的病理生理学。

DESCRIPTION (provided by applicant): 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.