Research Article Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension Magdalena Cristóbal-García, 1 Fernando E. García-Arroyo, 1,2 Edilia Tapia, 1,2 Horacio Osorio, 1,2 Abraham S. Arellano-Buendía, 1,2 Magdalena Madero, 1 Bernardo Rodríguez-Iturbe, 3 José Pedraza-Chaverrí, 4 Francisco Correa, 5 Cecilia Zazueta, 5 Richard J. Johnson, 6 and Laura-Gabriela Sánchez Lozada 1,2 1 Department of Nephrology, INC Ignacio Ch´ avez, 14080 Mexico City, DF, Mexico 2 Laboratory of Renal Physiopathology, INC Ignacio Ch´ avez, 14080 Mexico City, DF, Mexico 3 Division of Nephrology, Hospital Universitario de Maracaibo and Laboratory of Immunobiology, Instituto Venezolano Investigaciones Cient´ ıicas, Maracaibo 04011, Zulia, Venezuela 4 Department of Biology, Facultad de Qu´ ımica UNAM, 04510 Mexico City, DF, Mexico 5 Department of Cardiovascular Biomedicine, INC Ignacio Ch´ avez, 14080 Mexico City, DF, Mexico 6 Division of Renal Diseases and Hypertension, University of Colorado, Denver, CO 80045, USA Correspondence should be addressed to Laura-Gabriela S´ anchez Lozada; lgsanchezlozada@gmail.com Received 9 December 2014; Revised 6 March 2015; Accepted 7 March 2015 Academic Editor: Swaran J. S. Flora Copyright © 2015 Magdalena Crist´ obal-Garc´ ıa et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks) and short-term (3 weeks) efects of oxonic acid induced hyperuricemia were studied in rats (OA, 750mg/kg BW), OA+Allopurinol (AP, 150mg/L drinking water), OA+Tempol (T, 15 mg/kg BW), or vehicle. Systolic blood pressure, renal blood low, and vascular resistance were measured. Tubular damage (urine N-acetyl--D-glucosaminidase) and oxidative stress markers (lipid and protein oxidation) along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident. 1. Introduction Over recent years, epidemiological studies and clinical inter- vention trials, including randomized controlled trials, have shown that hyperuricemia is likely a cause or exacerbating factor of hypertension and progressive kidney disease [1–3]. Experimental studies demonstrated that experimental hyperuricemic hypertension is associated with inlammation, renal microvascular damage, and renal vasoconstriction [4– 8]. Oxidative stress seems to be a primary deletereous efect induced by increased uric acid (UA) [4]. In this regard, Hindawi Publishing Corporation Oxidative Medicine and Cellular Longevity Volume 2015, Article ID 535686, 8 pages http://dx.doi.org/10.1155/2015/535686