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The permeability-reducing effects of prostacyclin and inhibition of Rho kinase do not counteract endotoxin-induced increase in permeability in cat skeletal muscle.

Lundblad, Cornelia LU ; Bentzer, Peter LU and Grände, Per-Olof LU (2004) In Microvascular Research 68(3). p.286-294
Abstract
cAMP stimulation and Rho kinase inhibition are shown to decrease microvascular permeability during noninflammatory conditions, most likely by decreasing contractility of actomyosin filaments in the endothelial cell, but their effects on permeability during inflammatory conditions are not clarified. The objective of this in vivo study, performed on the autoperfused and denervated calf muscle of the cat, was therefore to evaluate to what extent cAMP stimulation and inhibition of Rho kinase reduce permeability at endotoxemia. Change in osmotic reflection coefficient for albumin was used as a measure of altered protein permeability and change in capillary filtration coefficient (CFC) as a measure of altered fluid permeability. After inducing a... (More)
cAMP stimulation and Rho kinase inhibition are shown to decrease microvascular permeability during noninflammatory conditions, most likely by decreasing contractility of actomyosin filaments in the endothelial cell, but their effects on permeability during inflammatory conditions are not clarified. The objective of this in vivo study, performed on the autoperfused and denervated calf muscle of the cat, was therefore to evaluate to what extent cAMP stimulation and inhibition of Rho kinase reduce permeability at endotoxemia. Change in osmotic reflection coefficient for albumin was used as a measure of altered protein permeability and change in capillary filtration coefficient (CFC) as a measure of altered fluid permeability. After inducing a significant increase in protein and fluid permeability by infusion of lipopolysaccharide (LPS), we determined to what extent the increased permeability was decreased by the cAMP stimulator prostacyclin [1.0 ng/kg/min intravenously (iv)] or the Rho kinase inhibitor Y-27632 [1.05 μg/ml plasma/h intraarterially (ia)]. These doses are known to decrease permeability under noninflammatory conditions. The reflection coefficient for albumin and CFC were determined before and during LPS, and during LPS plus prostacyclin (n = 6) or LPS plus Y-27632 (n = 6). The reflection coefficient was reduced by about 30% (P < 0.05) and CFC was increased by about 25% (P < 0.05) by LPS, and these permeability parameters were not affected by prostacyclin or Y-27632. We conclude that cAMP stimulation and Rho kinase inhibition reduce permeability by other pathways and mechanisms than those by which permeability is increased during endotoxemia. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Permeability, Endotoxemia, Sepsis, Rho kinase inhibition, Prostacyclin
in
Microvascular Research
volume
68
issue
3
pages
286 - 294
publisher
Academic Press
external identifiers
  • pmid:15501248
  • wos:000224910000016
  • scopus:14244251637
ISSN
1095-9319
DOI
10.1016/j.mvr.2004.07.002
language
English
LU publication?
yes
id
dfa27d30-c4bd-47bd-a3f2-27b742a8d0d8 (old id 129717)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15501248&dopt=Abstract
date added to LUP
2007-07-17 11:01:22
date last changed
2017-01-01 05:12:30
@article{dfa27d30-c4bd-47bd-a3f2-27b742a8d0d8,
  abstract     = {cAMP stimulation and Rho kinase inhibition are shown to decrease microvascular permeability during noninflammatory conditions, most likely by decreasing contractility of actomyosin filaments in the endothelial cell, but their effects on permeability during inflammatory conditions are not clarified. The objective of this in vivo study, performed on the autoperfused and denervated calf muscle of the cat, was therefore to evaluate to what extent cAMP stimulation and inhibition of Rho kinase reduce permeability at endotoxemia. Change in osmotic reflection coefficient for albumin was used as a measure of altered protein permeability and change in capillary filtration coefficient (CFC) as a measure of altered fluid permeability. After inducing a significant increase in protein and fluid permeability by infusion of lipopolysaccharide (LPS), we determined to what extent the increased permeability was decreased by the cAMP stimulator prostacyclin [1.0 ng/kg/min intravenously (iv)] or the Rho kinase inhibitor Y-27632 [1.05 μg/ml plasma/h intraarterially (ia)]. These doses are known to decrease permeability under noninflammatory conditions. The reflection coefficient for albumin and CFC were determined before and during LPS, and during LPS plus prostacyclin (n = 6) or LPS plus Y-27632 (n = 6). The reflection coefficient was reduced by about 30% (P &lt; 0.05) and CFC was increased by about 25% (P &lt; 0.05) by LPS, and these permeability parameters were not affected by prostacyclin or Y-27632. We conclude that cAMP stimulation and Rho kinase inhibition reduce permeability by other pathways and mechanisms than those by which permeability is increased during endotoxemia.},
  author       = {Lundblad, Cornelia and Bentzer, Peter and Grände, Per-Olof},
  issn         = {1095-9319},
  keyword      = {Permeability,Endotoxemia,Sepsis,Rho kinase inhibition,Prostacyclin},
  language     = {eng},
  number       = {3},
  pages        = {286--294},
  publisher    = {Academic Press},
  series       = {Microvascular Research},
  title        = {The permeability-reducing effects of prostacyclin and inhibition of Rho kinase do not counteract endotoxin-induced increase in permeability in cat skeletal muscle.},
  url          = {http://dx.doi.org/10.1016/j.mvr.2004.07.002},
  volume       = {68},
  year         = {2004},
}