Reversible angiotensin II-mediated albuminuria in rat kidneys is dynamically associated with cytoskeletal organization

Clavant, Steven P., Forbes, Josephine M., Thallas, Vicki, Osicka, Tanya M., Jerums, George and Comper, Wayne D. (2003) Reversible angiotensin II-mediated albuminuria in rat kidneys is dynamically associated with cytoskeletal organization. Nephron, 93 2: 51-60. doi:10.1159/000068528


Author Clavant, Steven P.
Forbes, Josephine M.
Thallas, Vicki
Osicka, Tanya M.
Jerums, George
Comper, Wayne D.
Title Reversible angiotensin II-mediated albuminuria in rat kidneys is dynamically associated with cytoskeletal organization
Journal name Nephron   Check publisher's open access policy
ISSN 0028-2766
2235-3186
Publication date 2003-02
Sub-type Article (original research)
DOI 10.1159/000068528
Open Access Status Not yet assessed
Volume 93
Issue 2
Start page 51
End page 60
Total pages 10
Place of publication Basel, Switzerland
Publisher S. Karger AG
Language eng
Formatted abstract
Angiotensin II (ANG II) is intimately involved in normal renal function, and is estimated to exist at a normal physiological range of 6-10 nM within the renal tubules. The potential role that intrarenal ANG II may play in renal disease was assessed by perfusing isolated rat kidneys with or without excess intratubular levels of ANG II, which may mimic changes in the intrarenal RAS under pathological conditions. The effects of increased systemic ANG II were also determined by infusing rats with ANG II by osmotic pump. In isolated perfused kidneys, ANG II significantly and specifically increased the fractional clearance of albumin to clinical levels, as determined by using radiolabelled albumin. This effect was reversible, as removing ANG II from the perfusate caused the albumin fractional clearance to decrease to pre-ANG II exposure levels. The increase in fractional clearance of albumin was not correlated with renal hemodynamic changes, nor glomerular permeability alterations as measured by the fractional clearance of 36 Å Ficoll and immunoglobulin G. Immunochemical analysis using anti-α-tubulin antibody of perfused kidney sections revealed that ANG II caused a marked disruption of tubular epithelial cytoskeletal components, through disassembly and reorganization of α-tubulin. This disruption was reversible. In vivo, osmotic pump delivery of ANG II at less potent dosage caused a proteinuria (Biuret) and an albuminuria (radioimmunoassay) in rats, from as early as 2 days after pump implantation. These results demonstrate that ANG II may reversibly induce clinical levels of albuminuria. These data point to an important role for renal tubules and the intratubular lumen concentrations of ANG II in the renal processing of albumin. 
Keyword Albumin fractional clearance
Angiotensin II
Glomerular permeability
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Mater Research Institute-UQ (MRI-UQ)
 
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