A High Salt Diet Increases Renal Nitrotyrosine Formation and Urinary Excretion of F 2 -Isoprostanes and Protein in Dahl Salt-Sensitive Rats

Abstract

P28 Superoxide formation causes tissue injury in many disease processes, and interaction between superoxide and nitric oxide forms peroxynitrite, a very strong oxidant. An index of peroxynitrite damage to tissues is nitrotyrosine formation. Also, F 2 -isoprostanes have been shown to be a reliable marker of oxidative stress in vivo. Recently, oxidative stress was shown to contribute to the maintenance of hypertension in the SHR; however, whether oxidative stress is involved in the renal damage that occurs in Dahl salt-sensitive (S) hypertension is not clear. Our goal was to determine the role of oxidative stress in the renal damage that occurs in Dahl S/Rapp rats on high Na intake by determining the urinary excretion of F 2 -isoprostanes and renal nitrotyrosine formation and determining urinary protein excretion as an index of renal damage. Studies were conducted in S rats on a low salt (0.3% NaCl) or a high salt (8% NaCl) diet for 3 weeks. After 3 weeks urine was collected continuously for 24 hours, and urinary F 2 -isoprostane concentration was measured with a gas chromatography/mass spectrometric assay. Renal nitrotyrosine formation was determined by immunohistochemistry and urinary protein excretion by the Bradford method. We found that high Na intake significantly increased urinary F 2 -isoprostane excretion to 24.2±1.7 ng/day compared with 9.7±0.8 ng/day in rats on a low Na diet, P<0.05. Renal glomerular nitrotyrosine was prevalent in the high Na group compared to the low Na group. Urinary protein excretion was 274±32 mg/day in high Na rats and 55±11 mg/day in low Na rats, P<0.05. The results suggest that oxidative stress is significantly increased in Dahl S rats on a high salt diet, which possibly contributes to the progression of renal damage.