Increased salt sensitivity induced by sensory denervation: role of superoxide.
OBJECTIVE
To test the hypothesis that production of superoxide in mesenteric resistance arteries is increased and contributes 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, decreased MAP in both CAP-HS and CON-HS when compared with their respective controls. However, the decreases of MAP between these 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, salt sensitive hypertension induced by sensory degeneration is associated with increased vascular superoxide production. Although tempol is incapable of preventing the development 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.
Song
Wei-zhong
WZ
Department of Medicine and Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA.
Chen
Alex F
AF
Wang
Donna H
DH
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003714:Denervation; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000201:enzymology; D009475:Neurons, Afferent / Q000187:drug effects; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017208:Rats, Wistar; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000009:adverse effects*; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism*
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D017673:Sodium Chloride, Dietary; D013113:Spin Labels; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D013482:Superoxide Dismutase; D002211:Capsaicin; C001803:tempol