Renal Humoral Factors In Renal Function & Hypertension

描述(申请人提供)：缺血性肾病是一个术语，描述了由于肾脏血流减少而引起的各种肾脏改变，特别是与肾血管性高血压(RVH)相关的肾脏改变。临床标准的评估或选择内科或外科治疗一直是巨大的困难，这主要是由于缺乏非侵入性程序来测量肾血流动力学的变化和狭窄(ST)和对侧(CONT)肾(KD)的肾小管液体流动。此外，不同的药物干预和手术干预的结果也不尽相同。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。正在测试的假设是，中度RVH代表血管紧张素II和液体容量保留之间的生理解偶联，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不可避免地伴随着容量耗竭，从而转移到维持高血压的肾素责任上。这项建议旨在通过使用最近开发的猪RVH模型来定义这些关系，在该模型中，使用高时间分辨率的三维断层扫描仪测量RBF(及其亚成分皮质血流量和髓质血流量)、GFR、近端和远端小管流体动力学。肾缺血的程度是通过用磁共振成像(MRI)测量血液中脱氧血红蛋白水平(BOLD技术)间接估计的。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来完成的。类似的技术也被用来评估经皮腔内肾血管成形术恢复ST-KD和COT-KD肾功能的有效性。最后，试图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，利用这种新技术在合适的猪肾血管性高血压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.