@article{APS6883,
author = {Hsiu-chu Chou and Liang-ti Huang and Tsu-fu Yeh and Chung-ming Chen},
title = {Rho-kinase inhibitor Y-27632 attenuates pulmonary hypertension in hyperoxia-exposed newborn rats},
journal = {Acta Pharmacologica Sinica},
volume = {34},
number = {10},
year = {2016},
keywords = {},
abstract = {Aim: To test the hypothesis that neonatal hyperoxia induced pulmonary hypertension accompanied by increased Rho-kinase expression in rat lungs and that Rho-kinase inhibitor could attenuate right ventricular hypertrophy and pulmonary arterial remodeling.
Methods: Newborn rats were exposed to >95% O2 in the first week after birth, then to 60% O2 in the following 2 weeks. Control pups were exposed to room air over the same periods. The pups were injected with either Rho-kinase inhibitor Y-27632 (10 mg·kg−1·d−1, ip) or vehicle from postnatal d 14 to 20. Lung and heart tissues were collected on postnatal d 7 and 21. Rho-kinase activity in lungs was measured using Western blotting and immunohistochemistry. The right ventricular hypertrophy and arterial medial wall thickness (MWT) were assessed morphologically.
Results: Rho-kinase activity in lungs was comparable between the hyperoxic and control pups on postnatal d 7, but it had a more than 2-fold increase in the hyperoxic pups on postnatal d 21. Moreover, the hyperoxic exposure induced structural features of pulmonary hypertension, as shown by the right ventricular hypertrophy and significantly increased arterial MWT. Administration with Y-27632 effectively blocked the hyperoxia-induced increase of Rho-kinase activity in lungs, and attenuated the right ventricular hypertrophy.
Conclusion: Rho-kinase inhibitor may be a novel therapy for attenuating the hyperoxia-induced structural changes in pulmonary hypertension.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/6883}
}