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This Article Full Text Full Text (PDF) All Versions of this Article: 289/6/L946    most recent 00188.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Sawafuji, M. Articles by Kobayashi, K. Search for Related Content PubMed PubMed Citation Articles by Sawafuji, M. Articles by Kobayashi, K.

Role of Rho-kinase in reexpansion pulmonary edema in rabbits

Departments of ¹Surgery and ²Medicine, Keio University School of Medicine, Tokyo; and ³Department of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine, Tochigi, Japan

Submitted 19 May 2004 ; accepted in final form 1 July 2005

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.

acute lung injury; acute respiratory distress syndrome; reexpansion pulmonary edema; Rho; Rho-kinase

This article has been cited by other articles:

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