Fetal pulmonary vascular remodeling in a rat model induced by hypoxia and indomethacin.
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.
Xu
Xue-Feng
XF
The Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, People's Republic of China.
Gu
Wei-Zhong
WZ
Wu
Xi-Ling
XL
Li
Ru-Yi
RY
Du
Li-Zhong
LZ
D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002317:Cardiovascular Agents; D004195:Disease Models, Animal; D004549:Elastin / Q000378:metabolism; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000150:complications; D007213:Indomethacin; D007231:Infant, Newborn; D008168:Lung / Q000098:blood supply / Q000378:metabolism; D009206:Myocardium / Q000473:pathology*; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010547:Persistent Fetal Circulation Syndrome / Q000097:blood / Q000139:chemically induced / Q000473:pathology*; D011651:Pulmonary Artery / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D002317:Cardiovascular Agents; D004549:Elastin; D007213:Indomethacin; D020097:Natriuretic Peptide, Brain; D052250:Nitric Oxide Synthase Type III; C495963:natriuretic peptide precursor type B, rat; C498862:Acta2 protein, rat; C496316:Nos3 protein, rat