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 mu g 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 +/- 86% 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). Conclusion: Candesartan ameliorates the adverse effect of endotoxin on the TGF component of dynamic autoregulation of RBF. Copyright (C) 2010 S. Karger AG, Basel