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.
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.
Authors: Prashob Porayette; Joshua F P van Amerom; Shi-Joon Yoo; Edgar Jaeggi; Christopher K Macgowan; Mike Seed Journal: Cardiol Young Date: 2014-06-16 Impact factor: 1.093