title: Interactions between oxidative stress and inflammation in salt-sensitive hypertension.
abstract: The goal of this study was to test the hypothesis that increases in oxidative stress in Dahl S rats on a high-salt diet help to stimulate renal nuclear factor-kappaB (NF-kappaB), renal proinflammatory cytokines, and chemokines, thus contributing to hypertension, renal damage, and dysfunction. We specifically studied whether antioxidant treatment of Dahl S rats on high Na intake would decrease renal inflammation and thus attenuate the hypertensive and adverse renal responses. Sixty-four 7- to 8-wk-old Dahl S or R/Rapp strain rats were maintained for 5 wk on high Na (8%) or high Na + vitamins C (1 g/l in drinking water) and E (5,000 IU/kg in food). Arterial and venous catheters were implanted at day 21. By day 35 in the high-Na S rats, antioxidant treatment significantly increased the renal reduced-to-oxidized glutathione ratio and decreased renal cortical H(2)O(2) and O(2)(*-) release and renal NF-kappaB. Antioxidant treatment with vitamins C and E in high-Na S rats also decreased renal monocytes/macrophages in the glomeruli, cortex, and medulla, decreased tumor necrosis factor-alpha by 39%, and decreased monocyte chemoattractant protein-1 by 38%. Vitamin-treated, high-Na S rats also experienced decreases in arterial pressure, urinary protein excretion, renal tubulointerstitial damage, and glomerular necrosis and increases in glomerular filtration rate and renal plasma flow. In conclusion, antioxidant treatment of high-Na Dahl S rats decreased renal inflammatory cytokines and chemokines, renal immune cells, NF-kappaB, and arterial pressure and improved renal function and damage.
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
authors.forename: N
authors.initials: N
authors.lastname: Tian
authors.forename: R S
authors.initials: RS
authors.lastname: Moore
authors.forename: S
authors.initials: S
authors.lastname: Braddy
authors.forename: R A
authors.initials: RA
authors.lastname: Rose
authors.forename: J-W
authors.initials: JW
authors.lastname: Gu
authors.forename: M D
authors.initials: MD
authors.lastname: Hughson
authors.forename: R D
authors.initials: RD
authors.lastname: Manning
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D018932:Chemokine CCL2; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011507:Proteinuria / Q000378:metabolism / Q000517:prevention & control; D051381:Rats; D020303:Rats, Inbred Dahl; D012079:Renal Circulation / Q000187:drug effects; D017673:Sodium Chloride, Dietary; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D000959:Antihypertensive Agents; D000975:Antioxidants; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D015850:Interleukin-6; D016328:NF-kappa B; D017673:Sodium Chloride, Dietary; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D014810:Vitamin E; D006861:Hydrogen Peroxide; D005978:Glutathione; D001205:Ascorbic Acid