title: Sympathoexcitation by brain oxidative stress mediates arterial pressure elevation in salt-induced chronic kidney disease.
abstract: 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.affiliation: Department of Nephrology and Endocrinology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. fujita-dis@h.u-tokyo.ac.jp
authors.forename: Megumi
authors.initials: M
authors.lastname: Fujita
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Ando
authors.forename: Hiroo
authors.initials: H
authors.lastname: Kawarazaki
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kawarasaki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Muraoka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtsu
authors.forename: Hideki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D018738:Hexamethonium / Q000494:pharmacology; D006977:Hypertension, Renal / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D057967:Infusions, Intraventricular; D008297:Male; D009392:Nephrectomy; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011507:Proteinuria / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D020303:Rats, Inbred Dahl; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000503:physiopathology*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D003497:Cyclic N-Oxides; D017382:Reactive Oxygen Species; D017673:Sodium Chloride, Dietary; D013113:Spin Labels; D013481:Superoxides; D018738:Hexamethonium; C001803:tempol