title: Tempol attenuates the development of hypertensive renal injury in Dahl salt-sensitive rats.
abstract: BACKGROUND
  Dahl salt-sensitive (DS) rats given a high-salt diet develop renal lesions that are virtually identical to those in human hypertensive nephrosclerosis and are associated with increased oxidative stress. This study looks at the effects of a superoxide scavenger in preventing of hypertensive renal damage in high-salt-treated DS rats.
  
  
  METHODS
  The DS rats (n = 5 per group) were treated with 0.3% NaCl diets (LS), 8% NaCl diets (HS), and 8% NaCl diets plus 10 mmol/L tempol in drinking water (HS+T) for 5 weeks. Systolic blood pressure (SBP) was measured by the tail-cuff method. As markers of renal damage, we measured serum creatinine, creatinine clearance, histopathologic indices, and transforming growth factor-beta1 (TGF-beta1; a mediator for renal fibrosis) expression. In addition, 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells and expression of heme oxygenase-1 (HO-1) were quantified as markers of oxidative stress.
  
  
  RESULTS
  We found that a high-salt diet (8% NaCl) led to the development of hypertension, increased oxidative stress in the renal tissue (8-OHdG immunoreactive staining and HO-1 protein expression), increased renal histopathologic damage (arteriosclerosis index, matrix score, and interstitial volume) accompanied by accumulation of TGF-beta1, and decreased creatinine clearance in the DS rats. These adverse effects of salt were prevented by the tempol supplementation.
  
  
  CONCLUSIONS
  Histopathologic and biochemical findings indicate that, in the DS rat, salt-induced hypertensive nephropathy is associated with increased oxidative stress. Superoxide mimetic tempol can reduce this detrimental effect of salt feeding through TGF-beta1 suppression and consequently prevent the development of hypertension and hypertensive nephropathy.
authors.affiliation: Division of Cardiovascular Medicine, Surugadai Nihon University Hospital, Tokyo, Japan. rhisaki@med.nihon-u.ac.jp
authors.forename: Ryohei
authors.initials: R
authors.lastname: Hisaki
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Fujita
authors.forename: Fumio
authors.initials: F
authors.lastname: Saito
authors.forename: Toshio
authors.initials: T
authors.lastname: Kushiro
mesh_terms: D000818:Animals; D006360:Heat-Shock Proteins / Q000032:analysis; D006419:Heme Oxygenase (Decyclizing); D006973:Hypertension / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress; D010105:Oxygenases / Q000032:analysis; D051381:Rats; D020303:Rats, Inbred Dahl; D012965:Sodium Chloride / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D013599:Systole; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D006360:Heat-Shock Proteins; D016212:Transforming Growth Factor beta; D013481:Superoxides; D012965:Sodium Chloride; D010105:Oxygenases; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat