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.