title: Salt-induced downregulation of renal aquaporins is prevented by losartan.
abstract: OBJECTIVE
  The purpose of this study was to investigate the expression of aquaporin-1 (AQP-1) and aquaporin-2 (AQP-2) in the renal tubule of rats fed with a high-salt diet and its modulation by the AT1 receptor blocker losartan.
  
  
  METHODS
  The experiments were performed in four groups of rats fed for 3 weeks with the following diets: regular rat chow (NS); high-salt (8% NaCl) chow (HS), NS plus losartan (NS-L) and HS plus losartan (HS-L). Losartan (40 mg x kg(-1)) was administered in the drinking water. Systolic blood pressure (SBP) and renal function were evaluated. The intrarenal levels of angiotensin II (Ang II), TGF-β(1), α-smooth muscle actin (α-SMA), endothelial nitric oxide synthase (eNOS), AQP-1 and AQP-2 were determined by immunohistochemistry. AQP-1 and AQP-2 protein levels were measured by western blot analysis.
  
  
  RESULTS
  A high-sodium diet downregulated AQP-1 and AQP-2 expression levels in the proximal tubule and collecting duct, respectively. The high-sodium diet also induced Ang II, TGF-β(1) and α-SMA overexpression and decreased eNOS expression in the renal cortex and medulla. Losartan increased the diuresis and natriuresis, favoring urinary sodium concentration. Additionally, losartan prevented the profibrogenic response, decreasing Ang II, TGF-β(1) and α-SMA levels and normalizing AQP-2 expression in the HS-L group. AQP-1 expression was upregulated by losartan in both the NS-L and HS-L groups.
  
  
  CONCLUSIONS
  These results show that increased intrarenal Ang II in rats fed with a high-salt diet downregulates renal AQP-1 and AQP-2 expressions. In addition, although losartan increased diuresis and natriuresis, it prevented the downregulation of aquaporins, favoring urinary sodium concentration.
authors.affiliation: Department of Pathophysiology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, INFIBIOC, CONICET, Buenos Aires, Argentina.
authors.forename: Silvana L
authors.initials: SL
authors.lastname: Della Penna
authors.forename: Gabriel
authors.initials: G
authors.lastname: Cao
authors.forename: Andrea
authors.initials: A
authors.lastname: Fellet
authors.forename: Ana M
authors.initials: AM
authors.lastname: Balaszczuk
authors.forename: Elsa
authors.initials: E
authors.lastname: Zotta
authors.forename: Carolina
authors.initials: C
authors.lastname: Cerrudo
authors.forename: Marcela
authors.initials: M
authors.lastname: Pandolfo
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Toblli
authors.forename: Belisario E
authors.initials: BE
authors.lastname: Fernández
authors.forename: Maria I
authors.initials: MI
authors.lastname: Rosón
mesh_terms: D000199:Actins / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism*; D051399:Aquaporin 2 / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D015536:Down-Regulation; D060766:Drinking Water / Q000008:administration & dosage; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009318:Natriuresis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000009:adverse effects*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D000804:Angiotensin II; D057912:Angiotensin II Type 2 Receptor Blockers; D051398:Aquaporin 1; D051399:Aquaporin 2; D060766:Drinking Water; D019808:Losartan; D052250:Nitric Oxide Synthase Type III; D044139:Receptor, Angiotensin, Type 2; D017673:Sodium Chloride, Dietary; D053773:Transforming Growth Factor beta1; C496022:Aqp1 protein, rat; C496025:Aqp2 protein, rat; C498862:Acta2 protein, rat; C496316:Nos3 protein, rat