Activation of the renin-angiotensin system in hyperoxia-induced lung fibrosis in neonatal rats.

BACKGROUND:Oxygen toxicity plays an important role in lung injury and may lead to bronchopulmonary dysplasia. We previously demonstrated that hyperoxia activated the renin-angiotensin system (RAS) in cultured human fetal lung fibroblasts. OBJECTIVE:To examine whether the upregulation of RAS components is associated with hyperoxia-induced lung fibrosis in neonatal Sprague-Dawley rats. METHODS:Experimental rat pups were exposed to 1 week of >95% O(2) and a further 2 weeks of 60% O(2). Control pups were exposed to room air over the same periods. Lung tissues were taken for biochemical and histochemical assays on postnatal days 7 and 21. RESULTS:Hyperoxia significantly increased total collagen content and the expression of type I collagen and alpha smooth muscle actin when compared to control rats. RAS components including angiotensinogen, angiotensin-converting enzyme, angiotensin II, and angiotensin II type 1 receptor were significantly upregulated by hyperoxia. The results also demonstrated that only the extracellular signal-regulated kinase (ERK) signaling pathway was activated by hyperoxia exposure. p38 mitogen-activated protein kinase and c-Jun N-terminal kinase were not activated. CONCLUSIONS:Local RAS activation is involved in the pathogenesis of hyperoxia-induced lung fibrosis in neonatal rats. ERK phosphorylation might mediate angiotensin II type 1 receptor activation.

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