title: Rosuvastatin prevents proteinuria and renal inflammation in nitric oxide-deficient rats.
abstract: OBJECTIVE
  The aim of the present study was to assess the effects of rosuvastatin on renal injury and inflammation in a model of nitric oxide deficiency.
  
  
  METHODS
  Male Wistar rats were randomly divided into four groups (n = 10/group) and treated for 28 days with saline (CTRL); 30 mg/kg/day L-NAME (L-name); L-NAME and 20 mg/kg/day rosuvastatin (L-name+ROS-20); or L-NAME and 2 mg/kg/day rosuvastatin (L-name+ROS-2). Systolic blood pressure was measured by plethysmography in the central artery of the tail. The serum total cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine, nitric oxide, interleukin-6, and tumor necrosis factor alpha levels were analyzed. Urine samples were taken to measure the albumin: urinary creatinine ratio. Kidneys were sectioned and stained with hematoxylin/eosin and Masson's trichrome. Immunohistochemical analysis of the renal tissue was performed to detect macrophage infiltration of the glomeruli.
  
  
  RESULTS
  The systolic blood pressure was elevated in the L-name but not the L-name+rosuvastatin-20 and L-name+rosuvastatin-2 groups. The L-name group had a significantly reduced nitric oxide level and an increased interleukin-6 and tumor necrosis factor alpha level, albumin: urinary creatinine ratio and number of macrophages in the renal glomeruli. Rosuvastatin increased the nitric oxide level in the L-name+rosuvastatin-2 group and reduced the interleukin-6 and tumor necrosis factor alpha levels, glomerular macrophage number and albumin:urinary creatinine ratio in the L-name+rosuvastatin-20 and L-name+rosuvastatin-2 groups.
  
  
  CONCLUSIONS
  Rosuvastatin treatment reduced glomerular damage due to improvement in the inflammatory pattern independent of the systolic blood pressure and serum lipid level. These effects may lead to improvements in the treatment of kidney disease.
authors.affiliation: Faculdade de Farmácia, Universidade Federal de Juiz de Fora, MG, Brazil. jgirardi@cardiol.br
authors.forename: Jose Marcos
authors.initials: JM
authors.lastname: Girardi
authors.forename: Rogerio Estevan
authors.initials: RE
authors.lastname: Farias
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Ferreira
authors.forename: Nadia Rezende Barbosa
authors.initials: NR
authors.lastname: Raposo
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004359:Drug Therapy, Combination / Q000379:methods; D005464:Fluorobenzenes / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007378:Interleukins / Q000097:blood; D007674:Kidney Diseases / Q000097:blood / Q000188:drug therapy*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D009393:Nephritis / Q000097:blood / Q000517:prevention & control*; D009569:Nitric Oxide / Q000097:blood / Q000172:deficiency*; D010991:Plethysmography; D011507:Proteinuria / Q000517:prevention & control*; D011743:Pyrimidines / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007378:Interleukins; D011743:Pyrimidines; D013449:Sulfonamides; D009569:Nitric Oxide; D000068718:Rosuvastatin Calcium; D019331:NG-Nitroarginine Methyl Ester