TY - JOUR
T1 - Role of Rho-kinase in reexpansion pulmonary edema in rabbits
AU - Sawafuji, Makoto
AU - Ishizaka, Akitoshi
AU - Kono, Mitsutomo
AU - Koh, Hidefumi
AU - Tasaka, Sadatomo
AU - Ishii, Yoshiki
AU - Kobayashi, Koichi
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/12
Y1 - 2005/12
N2 - Reexpansion of a collapsed lung increases the microvascular permeability and causes reexpansion pulmonary edema. Neutrophils and their products have been implicated in the development of this phenomenon. The small GTP-binding proteins Rho and its target Rho-kinase (ROCK) regulate endothelial permeability, although their roles in reexpansion pulmonary edema remain unclear. We studied the contribution of ROCK to pulmonary endothelial and epithelial permeability in a rabbit model of this disorder. Endothelial and epithelial permeability was assessed by measuring the tissue-to-plasma (T/P) and bronchoalveolar lavage (BAL) fluid-to-plasma (B/P) ratios with 125I-labeled albumin. After intratracheal instillation of 125I-albumin, epithelial permeability was also assessed from the plasma leak (PL) index, the ratio of 125I-albumin in plasma/total amount of instilled 125I- albumin. T/P, B/P, and PL index were significantly increased in the reexpanded lung. These increases were attenuated by pretreatment with Y-27632, a specific ROCK inhibitor. However, neutrophil influx, neutrophil elastase activity, and malondialdehyde concentrations in BAL fluid collected from the reexpanded lung were not changed by Y-27632. In endothelial monolayers, Y-27632 significantly attenuated the H2O2-induced increase in permeability and mitigated the morphological changes in the actin microfilament cytoskeleton of endothelial cells. These in vivo and in vitro observations suggest that the Rho/ROCK pathway contributes to the increase in alveolar barrier permeability associated with reexpansion pulmonary edema.
AB - Reexpansion of a collapsed lung increases the microvascular permeability and causes reexpansion pulmonary edema. Neutrophils and their products have been implicated in the development of this phenomenon. The small GTP-binding proteins Rho and its target Rho-kinase (ROCK) regulate endothelial permeability, although their roles in reexpansion pulmonary edema remain unclear. We studied the contribution of ROCK to pulmonary endothelial and epithelial permeability in a rabbit model of this disorder. Endothelial and epithelial permeability was assessed by measuring the tissue-to-plasma (T/P) and bronchoalveolar lavage (BAL) fluid-to-plasma (B/P) ratios with 125I-labeled albumin. After intratracheal instillation of 125I-albumin, epithelial permeability was also assessed from the plasma leak (PL) index, the ratio of 125I-albumin in plasma/total amount of instilled 125I- albumin. T/P, B/P, and PL index were significantly increased in the reexpanded lung. These increases were attenuated by pretreatment with Y-27632, a specific ROCK inhibitor. However, neutrophil influx, neutrophil elastase activity, and malondialdehyde concentrations in BAL fluid collected from the reexpanded lung were not changed by Y-27632. In endothelial monolayers, Y-27632 significantly attenuated the H2O2-induced increase in permeability and mitigated the morphological changes in the actin microfilament cytoskeleton of endothelial cells. These in vivo and in vitro observations suggest that the Rho/ROCK pathway contributes to the increase in alveolar barrier permeability associated with reexpansion pulmonary edema.
KW - Acute lung injury
KW - Acute respiratory distress syndrome
KW - Reexpansion pulmonary edema
KW - Rho
KW - Rho-kinase
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U2 - 10.1152/ajplung.00188.2004
DO - 10.1152/ajplung.00188.2004
M3 - Article
C2 - 16006483
AN - SCOPUS:27944481359
VL - 289
SP - L946-L953
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
SN - 1040-0605
IS - 6 33-6
ER -