Renal oxidative stress induced by long-term hyperuricemia alters mitochondrial function and maintains systemic hypertension.

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.

• Authors: Magdalena Cristóbal-García, Fernando E García-Arroyo, Edilia Tapia, Horacio Osorio, Abraham S Arellano-Buendía, Magdalena Madero, Bernardo Rodríguez-Iturbe, José Pedraza-Chaverrí, Francisco Correa, Cecilia Zazueta, Richard J Johnson, Laura-Gabriela Sánchez Lozada
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2015 Pg. 535686 ( 2015) ISSN: 1942-0994 [Electronic] United States
• PMID: 25918583 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Cyclic N-Oxides
• Spin Labels
• Oxonic Acid
• Allopurinol
• Adenosine Triphosphate
• tempol

Topics

• Adenosine Triphosphate (metabolism)
• Allopurinol (pharmacology)
• Animals
• Antioxidants (pharmacology)
• Blood Pressure (drug effects)
• Cyclic N-Oxides (pharmacology)
• Disease Models, Animal
• Hypertension (etiology, pathology)
• Hyperuricemia (chemically induced, complications, pathology)
• Kidney (blood supply, metabolism, pathology)
• Male
• Mitochondria (drug effects, metabolism)
• Oxidative Stress (drug effects)
• Oxonic Acid (toxicity)
• Oxygen Consumption
• Rats
• Rats, Sprague-Dawley
• Renal Circulation (drug effects)
• Spin Labels
• Time Factors