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Oxidative Medicine and Cellular Longevity
Volume 2015, Article ID 535686, 8 pages
http://dx.doi.org/10.1155/2015/535686
Research Article

Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

1Department of Nephrology, INC Ignacio Chávez, 14080 Mexico City, DF, Mexico
2Laboratory of Renal Physiopathology, INC Ignacio Chávez, 14080 Mexico City, DF, Mexico
3Division of Nephrology, Hospital Universitario de Maracaibo and Laboratory of Immunobiology, Instituto Venezolano Investigaciones Científicas, Maracaibo 04011, Zulia, Venezuela
4Department of Biology, Facultad de Química UNAM, 04510 Mexico City, DF, Mexico
5Department of Cardiovascular Biomedicine, INC Ignacio Chávez, 14080 Mexico City, DF, Mexico
6Division of Renal Diseases and Hypertension, University of Colorado, Denver, CO 80045, USA

Received 9 December 2014; Revised 6 March 2015; Accepted 7 March 2015

Academic Editor: Swaran J. S. Flora

Copyright © 2015 Magdalena Cristóbal-García et al. This 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.

Abstract

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) effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW), OA+Allopurinol (AP, 150 mg/L drinking water), OA+Tempol (T, 15 mg/kg BW), or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-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.