title: Atorvastatin prevents the downregulation of aquaporin-2 receptor after bilateral ureteral obstruction and protects renal function in a rat model.
abstract: OBJECTIVE
  To assess the effects of atorvastatin (ATORV) on renal function after bilateral ureteral obstruction (BUO), measuring inulin clearance and its effect on renal hemodynamic, filtration, and inflammatory response, as well as the expression of Aquaporin-2 (AQP2) in response to BUO and after the release of BUO.
  
  
  METHODS
  Adult Munich-Wistar male rats were subjected to BUO for 24 hours and monitored during the following 48 hours. Rats were divided into 5 groups: sham operated (n = 6); sham + ATORV (n = 6); BUO (n = 6); BUO + ATORV (10 mg/kg in drinking water started 2 days before BUO [n = 5]; and BUO + ATORV (10 mg/kg in drinking water started on the day of the release of BUO [n = 5]). We measured blood pressure (BP, mm Hg); inulin clearance (glomerular filtration rate [GFR]; mL/min/100 g); and renal blood flow (RBF, mL/min, by transient-time flowmeter). Inflammatory response was evaluated by histologic analysis of the interstitial area. AQP2 expression was evaluated by electrophoresis and immunoblotting.
  
  
  RESULTS
  Renal function was preserved by ATORV treatment, even if initiated on the day of obstruction release, as expressed by GFR, measured by inulin clearance. Relative interstitial area was decreased in both BUO + ATORV groups. Urine osmolality was improved in the ATORV-treated groups. AQP2 protein expression decreased in BUO animals and was reverted by ATORV treatment.
  
  
  CONCLUSIONS
  ATORV administration significantly prevented and restored impairment in GFR and renal vascular resistance. Furthermore, ATORV also improved urinary concentration by reversing the BUO-induced downregulation of AQP2. These findings have significant clinical implication in treating obstructive nephropathy.
authors.affiliation: Division of Urology, Department of Surgery, University of São Paulo School of Medicine, São Paulo, Brazil. alexandre.danilovic@sbu.org.br
authors.forename: Alexandre
authors.initials: A
authors.lastname: Danilovic
authors.forename: Roberto Iglesias
authors.initials: RI
authors.lastname: Lopes
authors.forename: Talita Rojas
authors.initials: TR
authors.lastname: Sanches
authors.forename: Maria Heloísa Massola
authors.initials: MH
authors.lastname: Shimizu
authors.forename: Fabíola M
authors.initials: FM
authors.lastname: Oshiro
authors.forename: Lúcia
authors.initials: L
authors.lastname: Andrade
authors.forename: Francisco Tibor
authors.initials: FT
authors.lastname: Dénes
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Seguro
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D000069059:Atorvastatin; D015536:Down-Regulation / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014517:Ureteral Obstruction / Q000503:physiopathology*
chemical_list: D051399:Aquaporin 2; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin