Neonatal Hyperoxia Induces Pulmonary Hypertension and Rho-kinase Expression in Rats

Background: Chronic oxygen exposure induces pulmonary hypertension in newborn rats. Rho-kinase is upregulated in animal models of hypoxia-induced pulmonary hypertension and Rho-kinase inhibitors decrease the pulmonary arterial pressure. Less is known about the response of Rho-kinase in hyperoxia-induced lung injury in neonates. A rat model of hyperoxia-induced pulmonary injury was established and the expression of Rho-kinase was also assessed in the lungs of newborn rats exposed to prolonged hyperoxia. Methods: Experimental rat pups were exposed to 1 wk of > 95% O2 and a further 2 wk of 60% O2. Control pups were exposed to room air over the same periods. Lung tissues were obtained for biochemical and histochemical assays on postnatal Day 21. Results: Hyperoxia significantly increased type I collagen mRNA expression and total collagen content on postnatal Day 21. Rho-kinase activity was measured as the ratio of phosphorylated ERM to ERM (ezrin, radixin, and moesin) and the ratio was significantly increased on postnatal Day 21 following hyperoxic exposure. Hyperoxic exposure for 3 wk also induced structural features of pulmonary hypertension, as indicated by increased right ventricular hypertrophy and arterial medial wall thickening. Conclusions: The results suggested that Rho-kinase might be involved in the pathogenesis of hyperoxia-induced pulmonary hypertension. (J Pediatr Resp Dis 2013;9:59-64)