title: Angiotensin II Type 1 Receptor Antagonism Attenuates Abnormalities in Dynamic Renal Blood Flow Autoregulation in Rats with Endotoxin-Induced Acute Kidney Injury.
abstract: BACKGROUND
  The aim was to examine the role of angiotensin II type 1 receptors in dynamic autoregulation of renal blood flow (RBF) in endotoxemia.
  
  
  METHODS
  Experiments were performed on anesthetized rats 16 h after intraperitoneal lipopolysaccharide (LPS) or vehicle administration. After baseline measurements, groups Sham-Saline, LPS-Saline and LPS-Candesartan received isotonic saline or candesartan (10 μg kg(-1) i.v.). Data were collected during eight consecutive 20-min clearance periods (C1-8). Transfer function (TF) analysis in the frequency domain was used to examine dynamic autoregulation of RBF.
  
  
  RESULTS
  Endotoxemic rats showed an approximate 50% reduction in glomerular filtration rate (GFR) and RBF (p < 0.05 vs. Sham-Saline). Candesartan significantly increased RBF (+40 ± 6% vs. baseline; p < 0.05) but did not significantly influence GFR. Endotoxemic animals showed a normal myogenic response but had elevated TF gain values in the frequency range of the tubuloglomerular feedback mechanism (TGF; 0.01-0.03 Hz) reflecting impaired autoregulation (periods C3-4, 2.2 ± 1.6 vs. -2.6 ± 0.6 dB, p < 0.05, and C7-8, -0.4 ± 1.3 vs. -4.0 ± 0.8 dB, p < 0.05; in groups LPS-Saline and Sham-Saline, respectively). Candesartan normalized TF gain in this frequency range (periods C7-8, -6.1 ± 2.3 dB in group LPS-Candesartan, p < 0.05 vs. LPS-Saline).
  
  
  CONCLUSIONS
  Candesartan ameliorates the adverse effect of endotoxin on the TGF component of dynamic autoregulation of RBF.
authors.affiliation: Departments of Anesthesiology and Intensive Care, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Nitescu
authors.forename: Gerald F
authors.initials: GF
authors.lastname: DiBona
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Grimberg
authors.forename: Gregor
authors.initials: G
authors.lastname: Guron
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004731:Endotoxins / Q000633:toxicity*; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D004731:Endotoxins