Role of Rho-kinase in reexpansion pulmonary edema in rabbits

Re-expansion 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 [sup.125I]-1abeled albumin. After intratracheal instillation of [sup.125I]-albumin, epithelial permeability was also assessed from the plasma leak (PL) index, the ratio of [sup.125I]-albumin in plasma/total amount of instilled [sup.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 [H.sub.2][O.sub.2]-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; re-expansion pulmonary edema; Rho; Rho-kinase