Role of Rho-kinase in reexpansion pulmonary edema in rabbits

Makoto Sawafuji, Akitoshi Ishizaka, Mitsutomo Kohno, Hidefumi Koh, Sadatomo Tasaka, Yoshiki Ishii, Koichi Kobayashi

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume289
Issue number6 33-6
DOIs
Publication statusPublished - 2005 Dec

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rho-Associated Kinases
Pulmonary Edema
Permeability
Rabbits
Albumins
Lung
Bronchoalveolar Lavage Fluid
Actin Cytoskeleton
Neutrophils
rho GTP-Binding Proteins
Leukocyte Elastase
Capillary Permeability
Malondialdehyde
Serum Albumin
Endothelial Cells
Y 27632

Keywords

  • Acute lung injury
  • Acute respiratory distress syndrome
  • Reexpansion pulmonary edema
  • Rho
  • Rho-kinase

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Role of Rho-kinase in reexpansion pulmonary edema in rabbits. / Sawafuji, Makoto; Ishizaka, Akitoshi; Kohno, Mitsutomo; Koh, Hidefumi; Tasaka, Sadatomo; Ishii, Yoshiki; Kobayashi, Koichi.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 289, No. 6 33-6, 12.2005.

Research output: Contribution to journalArticle

Sawafuji, Makoto ; Ishizaka, Akitoshi ; Kohno, Mitsutomo ; Koh, Hidefumi ; Tasaka, Sadatomo ; Ishii, Yoshiki ; Kobayashi, Koichi. / Role of Rho-kinase in reexpansion pulmonary edema in rabbits. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2005 ; Vol. 289, No. 6 33-6.
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