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Sympathoexcitation by Brain Oxidative Stress Mediates Arterial Pressure Elevation in Salt-Induced Chronic Kidney Disease.
MedLine Citation:
PMID:  22083162     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Hypertension is very prevalent in chronic kidney disease and critical for its prognosis. Sympathoexcitation and oxidative stress have been demonstrated to be involved in chronic kidney disease. We have shown previously that sympathoexcitation by brain oxidative stress mediates arterial pressure elevation in the salt-sensitive hypertension model, Dahl salt-sensitive rats. Thus, we investigated whether sympathoexcitation by excessive brain oxidative stress could contribute to arterial pressure elevation in salt-induced chronic kidney disease model rats. Young (3-week-old) male Sprague-Dawley rats were randomly assigned to a uninephrectomy or sham operation and then subjected to either a normal salt (0.5%) or high-salt (8.0%) diet for 4 weeks. The young salt-loaded uninephrectomized rats exhibited sympathoexcitation, hypertension, and renal injury, proteinuria and global glomerulosclerosis together with tubulointerstitial damage. Under urethane anesthesia and artificial ventilation, renal sympathetic nerve activity, arterial pressure, and heart rate decreased to a greater degree in the salt-loaded uninephrectomized rats than in the nonsalt-loaded uninephrectomized rats and the salt-loaded or nonsalt-loaded sham-operated rats, when Tempol, a membrane-permeable superoxide dismutase mimetic, was infused acutely into the lateral cerebral ventricle. Oxidative stress in the hypothalamus, measured by lucigenin chemiluminescence, was also significantly greater. Furthermore, in the salt-loaded uninephrectomized rats, antioxidant treatment with chronic intracerebroventricular Tempol decreased sympathetic nerve activity and arterial pressure, which, in turn, led to a decrease in renal damage. Similar effects were elicited by treatment with oral moxonidine, the central sympatholytic agent. In conclusion, sympathoexcitation by brain oxidative stress may mediate arterial pressure elevation in salt-induced chronic kidney disease.
Authors:
Megumi Fujita; Katsuyuki Ando; Hiroo Kawarazaki; Chiaki Kawarasaki; Kazuhiko Muraoka; Hiroshi Ohtsu; Hideki Shimizu; Toshiro Fujita
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-14
Journal Detail:
Title:  Hypertension     Volume:  -     ISSN:  1524-4563     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Departments of Nephrology and Endocrinology and Clinical Trial Data Management, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
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