title: Statin treatment reduces glomerular inflammation and   podocyte damage in rat deoxycorticosterone-acetate-salt   hypertension.
abstract: OBJECTIVE
  We examined the effects of fluvastatin treatment on the development of kidney injury in experimental deoxycorticosterone-acetate (DOCA)-salt hypertension.
  
  
  METHODS
  Male Sprague-Dawley rats underwent unilateral nephrectomy and received subcutaneous DOCA pellets as well as 1% NaCl for drinking. Simultaneously, rats were treated with 5 mg/kg per day fluvastatin, or solvent only for 6 weeks. Mean arterial pressure was measured intraarterially. Glomerulosclerosis, interstitial fibrosis, cell proliferation, inflammation and podocyte damage were evaluated on kidney sections. Inflammatory markers were measured by real-time PCR.
  
  
  RESULTS
  Mean arterial pressure was elevated in DOCA-salt-treated rats but unaltered by fluvastatin. Serum cholesterol was markedly elevated in DOCA-salt-treated rats and tended to be lower in fluvastatin-treated animals. Fluvastatin treatment decreased the mortality of DOCA-salt-treated rats. Urinary protein excretion, glomerular proliferation and macrophage infiltration as well as glomerulosclerosis were reduced by fluvastatin. Fluvastatin alleviated podocyte damage and glomerular osteopontin protein expression, which was localized in podocytes. On the contrary, interstitial fibrosis, inflammation and interstitial cell proliferation of DOCA-salt-treated rat kidneys were not influenced by fluvastatin.
  
  
  CONCLUSIONS
  Statin treatment reduces mortality and glomerular damage independent from blood pressure in a low-renin model of hypertensive nephrosclerosis. A reduction of podocyte damage and macrophage infiltration may explain the beneficial effects of fluvastatin.
authors.affiliation: Hospital for Children and Adolescents, Erlangen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hartner
authors.forename: Bernd
authors.initials: B
authors.lastname: Klanke
authors.forename: Nada
authors.initials: N
authors.lastname: Cordasic
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Roland E
authors.initials: RE
authors.lastname: Schmieder
authors.forename: Roland
authors.initials: R
authors.lastname: Veelken
authors.forename: Karl F
authors.initials: KF
authors.lastname: Hilgers
mesh_terms: D000818:Animals; D001794:Blood Pressure; D049109:Cell Proliferation; D003900:Desoxycorticosterone; D018450:Disease Progression; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology / Q000627:therapeutic use*; D000077340:Fluvastatin; D005921:Glomerulonephritis / Q000209:etiology / Q000517:prevention & control*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D008297:Male; D009400:Nephrosclerosis / Q000209:etiology / Q000517:prevention & control*; D009929:Organ Size; D050199:Podocytes / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D003900:Desoxycorticosterone; D000077340:Fluvastatin