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). Conclusion: Candesartan ameliorates the adverse effect of endotoxin on the TGF component of dynamic autoregulation of RBF.

Keywords:
Acute renal failure, Candesartan, Renal circulation, Sepsis, Transfer function analysis
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© 2010 S. Karger AG, Basel
2010
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