Role of Rho-kinase in reexpansion pulmonary edema in rabbits

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

Research output: Contribution to journalArticlepeer-review

16 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
Pages (from-to)L946-L953
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume289
Issue number6 33-6
DOIs
Publication statusPublished - 2005 Dec

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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