title: Salt-induced renal injury in SHRs is mediated by AT1 receptor activation.
abstract: OBJECTIVE
  This study aimed to examine the effects of salt loading, with or without simultaneous angiotensin receptor blocker (ARB) treatment, on the systemic and tissue renin-angiotensin system (RAS) in spontaneously hypertensive rats (SHRs).
  
  
  METHODS
  Evaluation was performed early (4 weeks) in the course of salt loading in order to examine initial mediating events of cardiovascular and renal damage produced by salt excess. Four groups of rats were studied. Group 1 received regular rat chow (normal-salt diet); group 2 received normal-salt diet and an ARB (losartan, 30 mg/kg per day); group 3 received high-salt (8%) chow; and group 4 received high-salt diet and losartan.
  
  
  RESULTS
  High-salt diet increased systolic pressure to 193±1 mmHg compared to 180±2 in normal-salt diet group. Losartan reduced SBP in SHRs fed normal-salt diet but did not reduce SBP in the SHRs fed high-salt diet (192±2 mmHg). High-salt diet markedly increased urinary protein excretion from 27±4 to 64±13 mg/day and this increase was ameliorated by losartan (40±9 mg/day). In SHRs on high-salt diet, plasma angiotensin II concentration increased three to four-fold, whereas urinary angiotensinogen excretion increased 10-fold; and these changes were significantly reduced by losartan. High-salt diet accelerated glomerular injury and interstitial fibrosis in SHRs which were reduced by losartan.
  
  
  CONCLUSIONS
  These results demonstrate that the activity of RAS was either not suppressed or, even augmented, after 4 weeks of salt loading despite high salt intake and increased SBP. The data suggest that an augmented intrarenal RAS during high-salt diet may contribute to the development of renal injury in this experimental model.
authors.affiliation: Hypertension Research Laboratory, Division of Research, Ochsner Clinic Foundation, New Orleans, Louisiana 70121, USA. dsusic@ochsner.org
authors.forename: Dinko
authors.initials: D
authors.lastname: Susic
authors.forename: Edward D
authors.initials: ED
authors.lastname: Frohlich
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.forename: Weijian
authors.initials: W
authors.lastname: Shao
authors.forename: Dale
authors.initials: D
authors.lastname: Seth
authors.forename: L Gabriel
authors.initials: LG
authors.lastname: Navar
mesh_terms: D000818:Animals; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists*; D017673:Sodium Chloride, Dietary / Q000633:toxicity*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D017673:Sodium Chloride, Dietary