%0 Journal Article %A Alvin H. Lee %A Crystal Kantores %A Julijana Ivanovska %A Charlotte Sewing %A Robert P. Jankov %T Rho-kinase inhibitor ameliorates bleomycin-induced chronic lung injury in neonatal rats %D 2011 %J European Respiratory Journal %P p4307 %V 38 %N Suppl 55 %X Bleomycin (BLEO) induces a chronic neonatal lung injury (CNLI) in rats that is characterized by inflammation, arrest of lung development and pulmonary hypertension (PHT), similar to severe bronchopulmonary dysplasia. Increased Rho-kinase (ROCK) signaling contributes to experimental inflammatory lung injury in adult animals but its role during early life remains unknown.Methods: Rat pups received BLEO (1 mg/kg/d i.p.) or saline vehicle from postnatal days 1-14 ± Y27632 (a ROCK inhibitor; 10 mg/kg/d i.p.). Inflammation was assessed by tissue counts of immunoreactive macrophages (CD68) and neutrophils (MPO). Chronic PHT was assessed by right ventricle/left ventricle+septum weight ratio and% medial wall thickness of pulmonary resistance arteries. Markers of lung growth, injury and alveolarization included weight, tissue fraction, mean linear intercept and secondary crest counts.Results: Lungs of BLEO-exposed pups had up-regulated ROCK activity, as evidenced by increased phosphorylation of ROCK targets, MYPT-1 and LIMK1, which was completely inhibited by Y27632. Treatment with Y27632 completely prevented neutrophil influx to the BLEO-exposed lung while having no effect on increased macrophages. Y27632 completely prevented BLEO-induced PHT and partially improved septal thinning, but did not affect inhibited lung growth or alveolarization. Complete abrogation of BLEO-mediated neutrophil influx by treatment with SB265610 (a CXCR2 antagonist; 4 mg/kg/d) had no effect on parenchymal or vascular injury.Conclusions: ROCK inhibition prevented chronic PHT and improved parenchymal injury (septal thinning) in BLEO-mediated CNLI, independent of changes in inflammatory cells. Funded by the CIHR. %U