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TRANSLATIONAL PHYSIOLOGY

Effect of renal medullary H₂O₂ on salt-induced hypertension and renal injury

Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin

Submitted 19 July 2005 ; accepted in final form 12 August 2005

ABSTRACT

Dahl salt-sensitive (SS) and consomic, salt-resistant SS-13^BN rats possess substantial differences in blood pressure salt-sensitivity even with highly similar genetic backgrounds. The present study examined whether increased oxidative stress, particularly H₂O₂, in the renal medulla of SS rats contributes to these differences. Blood pressure was measured using femoral arterial catheters in three groups of rats: 1) 12-wk-old SS and consomic SS-13^BN rats fed a 0.4% NaCl diet, 2) SS rats fed a 4% NaCl diet and chronically infused with saline or catalase (6.9 µg·kg^–1·min^–1) directly into the renal medulla, and 3) SS-13^BN fed high salt (4%) and infused with saline or H₂O₂ (347 nmol·kg^–1·min^–1) into the renal medullary interstitium. After chronic blood pressure measurements, renal medullary interstitial H₂O₂ concentration ([H₂O₂]) was collected by microdialysis and analyzed with Amplex red. Blood pressure and [H₂O₂] were both significantly higher in SS (126 ± 3 mmHg and 145 ± 17 nM, respectively) vs. SS-13^BN rats (116 ± 2 mmHg and 56 ± 14 nM) fed a 0.4% diet. Renal interstitial catalase infusion significantly decreased [H₂O₂] (96 ± 41 vs. 297 ± 52 nM) and attenuated the hypertension (146 ± 2 mmHg catalase vs. 163 ± 4 mmHg saline) in SS rats after 5 days of high salt (4%). H₂O₂ infused into the renal medulla of consomic SS-13^BN fed high salt (4%) for 7 days accentuated the salt sensitivity (145 ± 2 mmHg H₂O₂ vs. 134 ± 1 mmHg saline). [H₂O₂] was also increased in the treated group (83 ± 1 nM H₂O₂ vs. 44 ± 9 nM saline). These data show that medullary production of H₂O₂ may contribute to salt-induced hypertension in SS rats and that chromosome 13 of the Brown Norway contains gene(s) that protect against renal medullary oxidant stress.

SS-13^BN rats; salt sensitivity

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