title: Angiotensin II receptor blocker pretreatment of rats undergoing sudden renal ablation.
abstract: BACKGROUND
  Subtotal nephrectomy (N) in rats results in progressive hypertension, proteinuria and renal lesions. Renin-angiotensin system blockade initiated at N prevents these changes; treatments failing to reduce hypertension and proteinuria do not.
  
  
  METHODS
  Ten Munich-Wistar rats underwent 1&frac12; surgical N; eight littermates were pretreated with losartan (L) only for 6 weeks prior to 1&frac12; N (N + L). Pretreated (n = 8; C + L) and untreated controls (C; n = 8) had sham operations.
  
  
  RESULTS
  Over 6 months, N and N + L rats developed ∼80% increase in glomerular filtration rate per nephron over C and C + L, P < 0.001). Hypertension (intra-arterial mean blood pressure 116 ± 6.8 mmHg in N rats versus 102 ± 3.2 in C, 104 ± 8.4 in C + L, and 104 ± 8.4 in N + L rats, P < 0.001 for all) and proteinuria (120 ± 20 mg/day in N versus 39 ± 10 in C, 34 ± 8 in C + L and 35 ± 8 in N + L, P < 0.001 for all) developed only in N. Focal segmental glomerulosclerosis (FSGS) (%) at 6 months was 20 ± 8 in N and 17.5 ± 8 in N + L (ns) and <1 in C and C + L (P < 0.001 versus N and N + L). Interstitial fractional volume (Vv), 4.0 ± 1.7% in C and 4.4 ± 1.6% in C + L (ns), was similarly increased to 7.5 ± 2.5% in N and 9.0 ± 3.9% in N+L (P < 0.04 versus C and C + L). Atrophic tubule Vv was increased by >300% in N and N + L over C and C + L (P < 0.02 for all). Glomerular volume doubled in N and N + L (P < 0.001). Podocyte foot process effacement was greater in N and NL than in C or C + L (P ≤ 0.02 for all). Thus, L given for 6 weeks prior to 1&frac12; N prevented hypertension and proteinuria over the subsequent 6 months without reducing glomerular hypertrophy, hyperfiltration or interstitial, tubular or FSGS lesions or foot process effacement.
  
  
  CONCLUSIONS
  These studies dissociated systemic hypertension and proteinuria from the renal lesions in this model. Durable effects of losartan on blood pressure and proteinuria likely represent epigenetic processes.
authors.affiliation: Department of Pediatrics, Seoul National University Bundang Hospital, Sungnam, South Korea.
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Park
authors.forename: Youngki
authors.initials: Y
authors.lastname: Kim
authors.forename: Kee Hyuck
authors.initials: KH
authors.lastname: Kim
authors.forename: Silvia
authors.initials: S
authors.lastname: Rozen
authors.forename: Behzad
authors.initials: B
authors.lastname: Najafian
authors.forename: Michael
authors.initials: M
authors.lastname: Mauer
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D005919:Glomerular Filtration Rate; D006973:Hypertension / Q000209:etiology / Q000517:prevention & control*; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D007677:Kidney Function Tests; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009392:Nephrectomy / Q000009:adverse effects*; D011507:Proteinuria / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan