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Acute hyperglycemia induces rapid, reversible increases of glomerular permeability in non-diabetic rats.

Axelsson, Josefin LU ; Rippe, Anna LU and Rippe, Bengt LU (2010) In American Journal of Physiology-Renal Physiology1997-01-01+01:00 298(6). p.1306-1312
Abstract
This study was performed to investigate the impact of acute hyperglycemia (HG) on the permeability of the normal glomerular filtration barrier in vivo. In anaesthetized Wistar rats (250-280g), the left ureter was catheterized for urine collection, while simultaneously blood access was achieved. Rats received an intravenous (i.v.) infusion of either 1) hypertonic glucose to maintain blood glucose at 20-25 mM (G; n=8); 2) hypertonic glucose as in 1) and a Rho-A-kinase inhibitor (Y-27632; Rho-G; n=8); 3) 20% mannitol (MANN; n=7), or 4) hypertonic (12%) NaCl to maintain plasma crystalloid osmotic pressure (picry) at ~320-325 mOsm/l (NaCl; n=8); 5) physiologic saline (SHAM; n=8). Fluorescein isothiocyanate (FITC)-Ficoll 70/400 was infused i.v.... (More)
This study was performed to investigate the impact of acute hyperglycemia (HG) on the permeability of the normal glomerular filtration barrier in vivo. In anaesthetized Wistar rats (250-280g), the left ureter was catheterized for urine collection, while simultaneously blood access was achieved. Rats received an intravenous (i.v.) infusion of either 1) hypertonic glucose to maintain blood glucose at 20-25 mM (G; n=8); 2) hypertonic glucose as in 1) and a Rho-A-kinase inhibitor (Y-27632; Rho-G; n=8); 3) 20% mannitol (MANN; n=7), or 4) hypertonic (12%) NaCl to maintain plasma crystalloid osmotic pressure (picry) at ~320-325 mOsm/l (NaCl; n=8); 5) physiologic saline (SHAM; n=8). Fluorescein isothiocyanate (FITC)-Ficoll 70/400 was infused i.v. for at least 20 min before terminating the experiments, and plasma and urine collected to determine the glomerular sieving coefficients () for polydisperse Ficoll (mol. radius 15-80A) by high performance size exclusion chromatography. In G there was a marked increase in for Ficoll55-80A at 20 min, which was completely reversible within 60 min and abrogated by a Rho-kinase (ROCK) inhibitor, while glomerular permeability remained unchanged in MANN and NaCl. In conclusion, acute HG caused rapid, reversible increases in for large Ficolls, not related to the concomitant hyperosmolarity, but sensitive to ROCK inhibition. The changes observed were consistent with the formation of an increased number of large pores in the glomerular filter. The sensitivity of the permeability changes to ROCK inhibition strongly indicates that the cytoskeleton of the cells in the glomerular barrier be involved in these alterations. Key words: microalbuminuria, Rho-A-kinase, podocytes, endothelium. (Less)
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published
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in
American Journal of Physiology-Renal Physiology1997-01-01+01:00
volume
298
issue
6
pages
1306 - 1312
publisher
American Physiological Society
external identifiers
  • wos:000277916800003
  • pmid:20237233
  • scopus:77952703704
ISSN
1522-1466
DOI
10.1152/ajprenal.00710.2009
language
English
LU publication?
yes
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42acfefb-f2cb-4441-9418-12a0317428e5 (old id 1581961)
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http://www.ncbi.nlm.nih.gov/pubmed/20237233?dopt=Abstract
date added to LUP
2010-04-07 17:24:34
date last changed
2018-05-29 10:25:29
@article{42acfefb-f2cb-4441-9418-12a0317428e5,
  abstract     = {This study was performed to investigate the impact of acute hyperglycemia (HG) on the permeability of the normal glomerular filtration barrier in vivo. In anaesthetized Wistar rats (250-280g), the left ureter was catheterized for urine collection, while simultaneously blood access was achieved. Rats received an intravenous (i.v.) infusion of either 1) hypertonic glucose to maintain blood glucose at 20-25 mM (G; n=8); 2) hypertonic glucose as in 1) and a Rho-A-kinase inhibitor (Y-27632; Rho-G; n=8); 3) 20% mannitol (MANN; n=7), or 4) hypertonic (12%) NaCl to maintain plasma crystalloid osmotic pressure (picry) at ~320-325 mOsm/l (NaCl; n=8); 5) physiologic saline (SHAM; n=8). Fluorescein isothiocyanate (FITC)-Ficoll 70/400 was infused i.v. for at least 20 min before terminating the experiments, and plasma and urine collected to determine the glomerular sieving coefficients () for polydisperse Ficoll (mol. radius 15-80A) by high performance size exclusion chromatography. In G there was a marked increase in for Ficoll55-80A at 20 min, which was completely reversible within 60 min and abrogated by a Rho-kinase (ROCK) inhibitor, while glomerular permeability remained unchanged in MANN and NaCl. In conclusion, acute HG caused rapid, reversible increases in for large Ficolls, not related to the concomitant hyperosmolarity, but sensitive to ROCK inhibition. The changes observed were consistent with the formation of an increased number of large pores in the glomerular filter. The sensitivity of the permeability changes to ROCK inhibition strongly indicates that the cytoskeleton of the cells in the glomerular barrier be involved in these alterations. Key words: microalbuminuria, Rho-A-kinase, podocytes, endothelium.},
  author       = {Axelsson, Josefin and Rippe, Anna and Rippe, Bengt},
  issn         = {1522-1466},
  language     = {eng},
  number       = {6},
  pages        = {1306--1312},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology-Renal Physiology1997-01-01+01:00},
  title        = {Acute hyperglycemia induces rapid, reversible increases of glomerular permeability in non-diabetic rats.},
  url          = {http://dx.doi.org/10.1152/ajprenal.00710.2009},
  volume       = {298},
  year         = {2010},
}