Advanced

Glomerular hyperpermeability after acute unilateral ureteral obstruction : Effects of Tempol, NOS, RhoA, and Rac-1 inhibition

Dolinina, Julia LU ; Rippe, Anna LU ; Bentzer, Peter LU and Öberg, Carl M. LU (2018) In American Journal of Physiology - Renal Physiology 315(3). p.445-453
Abstract

It is well known that proteinuria following urinary tract obstruction is mainly of a tubular nature. However, it is unknown whether there are also changes in glomerular permeability. In this study, we compared glomerular sieving coefficients (θ) of polydisperse fluorescein isothiocyanate (FITC)-Ficoll 70/400 following a 120-or 180-min unilateral ureteral obstruction (UUO) in anesthetized Sprague-Dawley rats. Samples were collected from the obstructed kidney at 5, 15, and 30 min postrelease and analyzed by means of high-pressure size-exclusion chromatography. After 120-min UUO, mean θ for Ficoll70Å was increased (P < 0.01) from 2.2 ± 0.5 × 10−5 (baseline) to 10.6 ± 10 × 10−5 15 min postrelease (highest... (More)

It is well known that proteinuria following urinary tract obstruction is mainly of a tubular nature. However, it is unknown whether there are also changes in glomerular permeability. In this study, we compared glomerular sieving coefficients (θ) of polydisperse fluorescein isothiocyanate (FITC)-Ficoll 70/400 following a 120-or 180-min unilateral ureteral obstruction (UUO) in anesthetized Sprague-Dawley rats. Samples were collected from the obstructed kidney at 5, 15, and 30 min postrelease and analyzed by means of high-pressure size-exclusion chromatography. After 120-min UUO, mean θ for Ficoll70Å was increased (P < 0.01) from 2.2 ± 0.5 × 10−5 (baseline) to 10.6 ± 10 × 10−5 15 min postrelease (highest value). After 180-min UUO, mean θ for Ficoll70Å was further increased (P < 0.001) from 1.4 ± 0.5 × 10−5 (baseline) to 40 ± 10 × 10−5 at 5 min postrelease (highest value). Administration of a reactive oxygen species (ROS) scavenger (Tempol; 1 mg·kg−1·min−1) partly abrogated the permeability effects following 120-min UUO but not after 180 min. Moreover, administration of the RhoA kinase inhibitor Y-27632, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, or Rac-1 inhibition did not ameliorate glomerular hyperpermeability following 180-min UUO. We show, for the first time, that acute UUO results in marked elevations in glomerular permeability. In addition, our data suggest a time-dependent pathophysiology of UUO-induced hyperpermeability, where reactive oxygen species generation may play an important role in the early stages.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Filtration barrier, Glomerular, Pore model, Ureteral obstruction
in
American Journal of Physiology - Renal Physiology
volume
315
issue
3
pages
445 - 453
publisher
American Physiological Society
external identifiers
  • scopus:85052928875
ISSN
0363-6127
DOI
10.1152/ajprenal.00610.2017
language
English
LU publication?
yes
id
2a3a5b3a-c562-4e96-8cd0-74323c2c9649
date added to LUP
2018-10-12 09:22:38
date last changed
2019-10-15 06:47:53
@article{2a3a5b3a-c562-4e96-8cd0-74323c2c9649,
  abstract     = {<p>It is well known that proteinuria following urinary tract obstruction is mainly of a tubular nature. However, it is unknown whether there are also changes in glomerular permeability. In this study, we compared glomerular sieving coefficients (θ) of polydisperse fluorescein isothiocyanate (FITC)-Ficoll 70/400 following a 120-or 180-min unilateral ureteral obstruction (UUO) in anesthetized Sprague-Dawley rats. Samples were collected from the obstructed kidney at 5, 15, and 30 min postrelease and analyzed by means of high-pressure size-exclusion chromatography. After 120-min UUO, mean θ for Ficoll<sub>70Å</sub> was increased (P &lt; 0.01) from 2.2 ± 0.5 × 10<sup>−5</sup> (baseline) to 10.6 ± 10 × 10<sup>−5</sup> 15 min postrelease (highest value). After 180-min UUO, mean θ for Ficoll<sub>70Å</sub> was further increased (P &lt; 0.001) from 1.4 ± 0.5 × 10<sup>−5</sup> (baseline) to 40 ± 10 × 10<sup>−5</sup> at 5 min postrelease (highest value). Administration of a reactive oxygen species (ROS) scavenger (Tempol; 1 mg·kg<sup>−1</sup>·min<sup>−1</sup>) partly abrogated the permeability effects following 120-min UUO but not after 180 min. Moreover, administration of the RhoA kinase inhibitor Y-27632, the nitric oxide synthase inhibitor N<sup>G</sup>-nitro-<sub>L</sub>-arginine methyl ester, or Rac-1 inhibition did not ameliorate glomerular hyperpermeability following 180-min UUO. We show, for the first time, that acute UUO results in marked elevations in glomerular permeability. In addition, our data suggest a time-dependent pathophysiology of UUO-induced hyperpermeability, where reactive oxygen species generation may play an important role in the early stages.</p>},
  author       = {Dolinina, Julia and Rippe, Anna and Bentzer, Peter and Öberg, Carl M.},
  issn         = {0363-6127},
  keyword      = {Filtration barrier,Glomerular,Pore model,Ureteral obstruction},
  language     = {eng},
  number       = {3},
  pages        = {445--453},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology - Renal Physiology},
  title        = {Glomerular hyperpermeability after acute unilateral ureteral obstruction : Effects of Tempol, NOS, RhoA, and Rac-1 inhibition},
  url          = {http://dx.doi.org/10.1152/ajprenal.00610.2017},
  volume       = {315},
  year         = {2018},
}