Abstract-The goal of this study was to test the hypothesis that oxidative stress in Dahl salt-sensitive (SS) rats on a high-sodium intake contributes to the progression of renal damage, the decreases in renal hemodynamics, and the development of hypertension. We specifically studied whether antioxidant therapy, using vitamins C and E, could help prevent renal damage and glomerular filtration rate (GFR) and renal plasma flow reductions and attenuate the increases in arterial pressure. Thirty-three 7-to 8-week old Dahl SS/Rapp strain rats were placed on either a high-sodium (8%) or a low-sodium (0.3%) diet with or without vitamin E (111 IU/d) in the food and 98 mg/d vitamin C in the drinking water for 5 weeks. Rats were equipped with indwelling arterial and venous catheters at day 21. By day 35 in the rats with high-sodium diet, vitamin C and E treatment significantly decreased renal cortical and medullary O 2 ⅐Ϫ release, mean arterial pressure, urinary protein excretion, glomerular necrosis, and renal tubulointerstitial damage. At this time, GFR significantly decreased in the high-sodium diet group (1.6Ϯ0.2 mL/min) when compared with either the high-sodium plus vitamins C and E (2.9Ϯ0.2 mL/min) or the low-sodium diet group (2.9Ϯ0.3 mL/min). In SS rats on high-sodium diet, renal plasma flow decreased 40%, and this reduced flow was restored by vitamin treatment. In Dahl salt-sensitive hypertension, increased oxidative stress plays an important role in the renal damage, decreases in renal hemodynamics, and increases in arterial pressure that occur. Antioxidant treatment with vitamins C and E improves renal dysfunction, lessens renal injury, and decreases arterial pressure in Dahl salt-sensitive hypertension. Key Words: antioxidants Ⅲ hemodynamics Ⅲ hypertension Ⅲ renal disease H ypertension continues to be a major cardiovascular risk factor and a major contributor to end-stage renal disease (ESRD). In particular, patients with salt-sensitive hypertension are much more likely to experience ESRD compared with salt-insensitive hypertensive patients. 1 Recent studies in humans and in animal models of salt-sensitive hypertension indicate that an increase in oxidative stress is associated with a progressive elevation in arterial pressure and a reduction in renal function. However, the mechanisms underlying the progression of hypertension and ESRD in salt-sensitive hypertension are not clear.A model that closely mimics human salt-sensitive essential hypertension is the Dahl S rat. Common traits shared by salt-sensitive humans and the S rat include progressive increases in arterial pressure and renal damage, 2,3 increased O 2 ⅐Ϫ release, 4 and endothelial dysfunction. 5 Recently, we have shown that the oxidative stress that occurs in Dahl S rats on high-sodium intake for 3 weeks contributes to the increase in arterial pressure, but renal hemodynamics were unchanged in high-sodium diet rats and renal damage was minor. 6 In contrast, renal damage is much more severe in S rats on high-sodium diet for 5 weeks, with progressive ...