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.
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