title: A 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor reduces hypertensive nephrosclerosis in stroke-prone spontaneously hypertensive rats.
abstract: BACKGROUND
  Recent studies suggest that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors (statins) exert their protective effects against cardiovascular diseases independently of their cholesterol-decreasing effects.
  
  
  OBJECTIVE
  To clarify the effect of a statin on hypertensive nephrosclerosis.
  
  
  METHODS
  We treated stroke-prone spontaneously hypertensive rats (spSHRs) chronically, starting at the age of 4 weeks, with cerivastatin (2 mg/kg per day by gavage) or vehicle. Physiological parameters, plasma chemistry and urine protein excretion were analysed. At 14 weeks of age, the rats had their kidneys removed for use in assays.
  
  
  RESULTS
  Compared with vehicle treatment, statin treatment reduced proteinuria and renal injury independently of blood pressure and cholesterol concentrations in spSHRs. Although expression of adhesion molecules and infiltration of inflammatory cells were not different whether or not cerivastatin treatment was used, renal fibrosis was significantly reduced in statin-treated spSHRs. We also found that expression of transforming growth factor-beta1 in kidneys was significantly inhibited in statin-treated spSHRs.
  
  
  CONCLUSIONS
  Cerivastatin prevents or retards hypertension-induced renal injury via inhibition of renal fibrosis and proteinuria. These results show the potential of statins as protective tools against proteinuric renal diseases, independent of their cholesterol-decreasing effects.
authors.affiliation: Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamashita
authors.forename: Seinosuke
authors.initials: S
authors.lastname: Kawashima
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Miwa
authors.forename: Masanori
authors.initials: M
authors.lastname: Ozaki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Namiki
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Hirase
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Inoue
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000150:complications*; D007249:Inflammation / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000097:blood; D008297:Male; D009400:Nephrosclerosis / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics; D011921:Rats, Inbred WKY; D020521:Stroke / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1