Renal Humoral Factors In Renal Function & Hypertension

描述（由申请人提供）：缺血性肾病是一个术语，描述由肾脏血流量减少引起的各种肾脏改变，特别是与肾血管性高血压（RVH）有关。评估这种疾病的临床标准或选择药物或手术治疗一直存在巨大困难，这主要是由于缺乏测量狭窄（ST）和对侧（CONT）肾脏（KD）肾脏血流动力学和小管流体流动变化的无创手术。此外，不同的药物干预以及手术干预的结果产生了不同的结果。这是由于缺乏关于血管紧张素II （ang II）、氧化应激（OX-ST）和内皮素（ET）在不同程度和慢性RVH中的相对参与的信息。正在验证的假设是，中度RVH代表血管紧张素II和体液潴留之间的生理解耦，这突出了OX-ST和ET在高血压维持中的作用。相比之下，严重的RVH不可避免地伴随着体积的减少，从而转向肾素维持高血压的责任。本研究旨在通过使用最近开发的猪RVH模型来定义这些关系，其中RBF（及其亚组分皮质血流和髓质血流）、GFR、近端和远端小管流体动力学用高时间分辨率的三维断层扫描仪测量。通过磁共振成像（MRI）间接测量血液中脱氧血红蛋白（BOLD技术）的水平来估计肾缺血的程度。ang II或OX-ST和ET的参与是通过使用该过程的特异性拮抗剂抑制剂来完成的。类似的技术被用于评估经皮腔内肾血管成形术在ST-和contkd患者中恢复肾功能的有效性。最后，尝试看看这项技术是否适用于患有肾血管性高血压的人。我们相信，通过这种新技术在肾血管性高血压猪模型中获得的信息将为临床医生提供强大的工具，因为它将显著改善缺血性肾病的诊断、治疗和随访。

DESCRIPTION (provided by applicant): Ischemic nephropathy is a term that describes a variety of renal alterations produced by a decrease of blood flow to the kidney, particularly in association with renovascular hypertension (RVH). The clinical criteria to assess this disease or to select medical or surgical treatment has been plagued by enormous difficulties which are mainly determined by the lack of noninvasive procedures to measure changes in renal hemodynamics and in tubular fluid flow in both the stenotic (ST) and the contralateral (CONT) kidney (KD). Moreover, the outcome of different pharmacological interventions as well as surgical interventions has yield disparate results. This is due to the lack of information about the relative participation of angiotensin II (ang II), oxidative stress (OX-ST), and endothelin (ET) during different degrees and chronicity of RVH. The hypothesis being tested is that moderate RVH represents a physiological uncoupling between angiotensin II and fluid volume retention which gives prominence to OX-ST and ET in the maintenance of hypertension. In contrast, severe RVH is inevitably accompanied by volume depletion that shifts toward renin the responsibility of maintaining hypertension. This proposal intends to define these relationships by using a recently developed swine model of RVH in which RBF (and its subcomponents cortical blood flow and medullary blood flow), GFR, proximal- and distal-tubule fluid dynamics are measured with a three dimensional tomographer with high temporal resolution. The degree of renal ischemia is estimated, indirectly by measuring blood levels of deoxyhemoglobin (BOLD technique) with magnetic resonance imaging (MRI). The participation of ang II or OX-ST and ET are done by using the specific antagonistinhibitors of this process. Similar techniques are used to evaluate the effectiveness of percutaneous transluminal renal angioplasty to restitute renal function in both ST- and CONT-KD's. Finally, an attempt is made to see if this technology is applicable to humans suffering from renovascular hypertension. We believe that the information obtained with such a novel technology in appropriate swine models of renovascular hypertension will provide the clinicians with formidable tools because it will significantly improve the diagnosis, treatment, and follow up of ischemic nephropathy.