AIM: To test the hypothesis that production of superoxide in mesenteric resistance arteries is increased and con- tributes to the development of hypertension induced by sensory denervation plus high salt intake. METHODS: Newborn Wistar rats were given capsaicin 50 mg/kg sc on the 1st and 2nd d of life. After weaning, male rats were grouped as follows and treated for 3 weeks with: capsaicin pretreatment plus normal sodium diet (0.5 %, CAP-NS), CAP plus high sodium diet (4 %, CAP-HS), control plus NS (CON-NS), or CON-HS. Both tail-cuff systolic blood pressure and mean arterial pressure (MAP) were measured in each of the groups. Western blot analysis was used for measurement of manganese superoxide dismutase (MnSOD) and endothelial nitric oxide synthase (eNOS) in the mesenteric resistance arteries. Lucigenin chemiluminescence assay was used for superoxide production in the mesenteric resistance arteries. The Griess method was used for measurement of nitrite/nitrate levels in plasma. RESULTS: Both tail-cuff pressure and MAP were higher in CAP-HS compared with CAP-NS, CON-HS, and CON- NS rats (P<0.05). Both MnSOD and eNOS in the mesenteric resistance arteries were increased in CAP-HS compared with CAP-NS, CON-HS, and CON-NS (P<0.05). However, nitrite/nitrate levels in plasma were not different among 4 groups. Acute iv administration of tempol, a membrane-permeable superoxide scavenger, de- creased MAP in both CAP-HS and CON-HS when compared with their respective controls. However, the de- creases of MAP between these two groups were not different. Chronic treatment with tempol failed to prevent the development of hypertension in CAP-HS rats. Superoxideproduction in the mesenteric resistance arteries was increased in CAP-HS compared with CAP-NS, CON-HS, and CON-NS (P<0.05). However, chronic treatment with tempol did not prevent the increase of mesenteric superoxideproduction in CAP-HS rats. CONCLUSIONS: Regardless of increased vascular MnSOD levels, salt sensitive hypertension induced by sensory degeneration is associated with increased vascular superoxide production. Although tempol is incapable of preventing the develop- ment of hypertension in sensory denervated rats fed a high salt diet, increased superoxide levels may contribute to exacerbated vascular impairment which may take longer time to develop. Given that superoxide may be produced by sources other than mitochondrion, future studies using other inhibitors (eg, inhibitors of NADPH oxidase and xanthine oxidase) may unveil the effectiveness of reducing superoxide on lowering blood pressure in this model. AIM: To test the hypothesis that production of superoxide in mesenteric resistance arteries is increased and con- tributes to the development of hypertension induced by sensory denervation plus high salt intake. METHODS: Newborn Wistar rats were given capsaicin 50 mg / kg sc on the 1st After 2nd and 2nd d of life. After weaning, male mice were grouped as follows and treated for 3 weeks with: capsaicin pretreatment plus normal sodium diet (CAP-NS), CAP plus high sodium diet (4% , both control-NS (CON-NS), or CON-HS. Both tail-cuff systolic blood pressure and mean arterial pressure (MAP) were measured in each of the groups. Western blot analysis was used for measurement of manganese superoxide dismutase (MnSOD ) and endothelial nitric oxide synthase (eNOS) in the mesenteric resistance arteries. Lucigenin chemiluminescence assay was used for superoxide production in the mesenteric resistance arteries. The Griess method was used for measurement of nitrite / nitrate levels in plasm RESULTS: Both tail-cuff pressure and MAP were higher in CAP-HS compared with CAP-NS, CON-HS, and CON-NS rats (P <0.05). Both MnSOD and eNOS in the mesenteric resistance arteries were increased in CAP-HS compared with CAP-NS, CON-HS, and CON-NS (P <0.05). However, nitrite / nitrate levels in plasma were not different among 4 groups. Acute iv administration of tempol, a membrane-permeable superoxide scavenger However, the de creases of MAP between both two groups were not different. Chronic treatment with tempol failed to prevent the development of hypertension in CAP -HS rats. Superoxide production in the mesenteric resistance arteries was increased in CAP-HS compared with CAP-NS, CON-HS, and CON-NS (P <0.05). However, chronic treatment with tempol did not prevent the increase of mesenteric superoxide production in CAP-HS rats. CONCLUSIONS: Regardless of increased vascular MnSOD levels, saltsensitive hypertension induced by sensory degeneration is associated with increased vascular superoxide production. Although tempol is incapable of preventing the develop- ment of hypertension in sensory denervated rats fed a high salt diet, increased superoxide levels may contribute to exacerbated vascular impairment which may take longer time to develop. Given that superoxide may be produced by sources other than mitochondrion, future studies using other inhibitors (eg, inhibitors of NADPH oxidase and xanthine oxidase) may unveil the effectiveness of reducing superoxide on lowering blood pressure in this model.