For years the diagnosis, .evaluation of renal function and the treatment of renovascular hypertension hasbeen the subject of intense debate. Most of these uncertainties are due to the lack of important informationabout the changes in intrarenal hemodynamics, glomerular filtration rate and proximal and distal tubularfunction in the stenotic kidney (ST-KD) as well as in the contralateral kidney (CONT-KD). Renal clearancesare not useful in these conditions because of mixture of urine in the bladder whereas independentcatheterization of ureters (split renal function) lead to pyelonephritis. In this proposal we intend to answerthese questions by using a novel three-dimensional tomographer with high temporal resolution thatmeasures accurately individual kidney blood flow (including cortical and medullary flow), proximal loop ofHenle and distal tubular fluid flow and fluid reabsorption. Actual renal ischemia is measured in each kidneyby estimating with magnetic resonance imaging (MRI), blood (capillary) oxygen (O2) levels ofdeoxyhemoglobin (BOLD technique). In the kidney O2 consumption is determined by sodium (Na)reabsorption in distal tubules by Na, K ATPase. Its inhibition with furosemide suppress O2 consumption(FSOC) and decrease blood levels of deoxyhemoglobin. The proposal contains three specific aims. In thefirst, the hypothesis to be tested is that the degree of arterial obstruction will determine a) the stage offunctional deficit in the ST-KD; b) the degree of increase in blood pressure; and c) the functionalcompensation reaction (hypertrophy) of the CONT-KD. These different responses will correlate with eitherincreases (CONT-KD) or decreases (ST-KD) of Na delivery and O2 consumption in distal nephrons. Thesecond specific aim tests the hypothesis that the efficacy of PTRA to restore renal function is determined bya) the degree of atrophy and functional decline in the ST-KD; b) the amount of ST-KD function that has beentransferred to CONT-KD; c) the degree of hypertension; and d) the inability of furosemide to induce O2suppression. This study will define the conditions under which PTRA is successful in recovering renalfunction in both the ST- and CONT-KD. Finally, the third specific aims, tests the hypothesis thatnormalization of hypertension by medical treatment significantly aggravates the function of the ST-KD butmay be beneficial to recover CONT-KD function. The conditions under which the CONT-KD may benefitfrom medical treatment are related to the possible reversal of vascular hyperplasia in preglomerulararterioles and that residual circulation is sufficient to meet the metabolic demands of tubular hypertrophy. It isalso assumes that anti-hypertensives that suppress the production of angiotensin II or oxidative stress will bemore effective in reversal of renal function to normal than non-specific vasodilators. Elucidation of all theseissues will have enormous clinical repercussion in the diagnosis, follow up, and treatment of renovascularhypertension.
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