Related Experiment Video
Updated: Jun 13, 2026
Establishment and Validation of a Rat Model of Pulmonary Arterial Hypertension Associated with Pulmonary Fibrosis
Published on: May 23, 2025
Fetal pulmonary vascular remodeling in a rat model induced by hypoxia and indomethacin
Xue-Feng Xu1, Wei-Zhong Gu, Xi-Ling Wu
1The Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, People's Republic of China.
Objective:
This study sought to determine the effect of combined treatment of hypoxia plus indomethacin on pulmonary vascular remodeling in fetal rats.
Methods:
Hypoxia and indomethacin were used to treat pregnant rats during 19-21 days of gestation. The adventitia, media, and intima of pulmonary arteries from fetal rats were assessed. Western blots were used for determining the abundance of smooth muscle specific alpha-actin protein (α-SMA), elastin, and endothelial nitric oxide synthase (eNOS) in lung tissues. Plasma brain-type natriuretic peptide (BNP) levels, reflecting the increased right ventricular load or pulmonary arterial pressure, were detected.
Results:
The ratio of left ventricular free wall plus septum to right ventricular weight significantly increased in hypoxia plus indomethacin-treated group. The medial thickness percentage of pulmonary arteries of < 100 μm and ≥100 μm in diameter from hypoxia plus indomethacin-treated group was higher than that from control or single treatment group. Vascular elastin area percentage and immunostaining density of eNOS from the combined-treated group were higher than other groups. The relative abundance of α-SMA, elastin, and eNOS and plasma BNP levels in hypoxia plus indomethacin-treated group also significantly increased compared with other groups.
Conclusions:
Hypoxia and indomethacin had synergistic effect on fetal pulmonary vascular remodeling. This rat model induced by combined treatments can mimic human persistent pulmonary hypertension of the newborn.
