Angiotensin II Type 1 Receptor Antagonism Attenuates Abnormalities in Dynamic Renal Blood Flow Autoregulation in Rats with Endotoxin-Induced Acute Kidney Injury.
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.
Nitescu
Nicoletta
N
Departments of Anesthesiology and Intensive Care, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden.
DiBona
Gerald F
GF
Grimberg
Elisabeth
E
Guron
Gregor
G
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
D047228:Angiotensin II Type 1 Receptor Blockers; D004731:Endotoxins