BACKGROUND: Effects of oxidative stress on the development of deoxycorticosterone acetate (DOCA)-salt or N(G)-nitro-L-arginine (L-NAME) hypertension were examined. METHODS: Male Sprague-awley rats were treated with DOCA (200 mg/kg, subcutaneous)-salt or L-NAME (40 mg/L in daily drinking water) for 4 weeks. To reduce the oxidative stress, 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol, 3 mM/L) was cotreated in drinking water. The expression of endothelial nitric oxide synthase (eNOS) and nitrotyrosine proteins was determined in the renal cortex and thoracic aorta. RESULTS: Tempol prevented the development of DOCA-salt hypertension, whereas it was without effect on L-NAME hypertension. In DOCA-salt hypertension, the eNOS expression in the renal cortex was increased, the degree of which was attenuated by Tempol. The renal expression of nitrotyrosine was decreased, which was further decreased by Tempol. In the aorta, the expression of both eNOS and nitrotyrosine was decreased, which was not further affected by Tempol. In L-NAME hypertension, the renal expression of eNOS was significantly increased, which was blocked by Tempol. The expression of eNOS in the aorta was slightly decreased, and was not further affected by Tempol. The renal expression of nitrotyrosine was not significantly altered. However, its expression was significantly decreased in the aorta, and was further reduced by Tempol. CONCLUSION: The blockade of oxidative stress may attenuate the development of hypertension and provide tissue protection in DOCA-salt hypertension. The blockade of oxidative stress may also contribute to a tissue protection in L-NAME hypertension.