BACKGROUND: In congenital diaphragmatic hernia (CDH), pulmonary hypertension increases right ventricle (RV) afterload, which could impair heart function and contribute to poor outcome for most affected infants. Nevertheless, the real significance of vascular pulmonary alterations in perinatal hemodynamics is largely unknown. It is defined that ventricular pressure overload induces increased myocardium gene expression of B-type natriuretic peptide (BNP) and components of the renin-angiotensinogen and endothelin (ET)-1 systems. Our aim was to evaluate perinatal myocardium expression of these genes associated with ventricular pressure overload in a nitrofen-induced CDH rat model. METHODS: In the nitrofen-induced CDH rat model, fetuses from dated pregnant Sprague-Dawley rats at 15.5, 17.5, 19.5 and 21.5 days postcoitum as well as newborn pups were assigned to 3 experimental groups: control, nitrofen (exposed to nitrofen, without CDH), and CDH (exposed to nitrofen, with CDH). Myocardial samples collected from the RV and left ventricle (LV) were processed for quantification of messenger RNA (mRNA) of BNP, angiotensinogen, and ET-1. RESULTS: The perinatal expression of BNP, angiotensinogen, and ET-1 mRNA in the RV and LV of the control group revealed daily changes. During gestation, the expression of BNP and angiotensinogen mRNA underwent significant oscillation compared with control in both nitrofen-exposed fetuses, although we cannot identify significant differences between the nitrofen and CDH groups. After birth, we found a significant increasing expression of all studied genes only in the RV of CDH pups. CONCLUSIONS: Perinatal myocardial quantification of BNP, angiotensinogen, and ET-1 mRNA levels suggests that both nitrofen-exposed and control pups revealed prenatal variations of expression of the studied genes. Moreover, CDH is associated with significant molecular alterations only in the RV after birth.
BACKGROUND: In congenital diaphragmatic hernia (CDH), pulmonary hypertension increases right ventricle (RV) afterload, which could impair heart function and contribute to poor outcome for most affected infants. Nevertheless, the real significance of vascular pulmonary alterations in perinatal hemodynamics is largely unknown. It is defined that ventricular pressure overload induces increased myocardium gene expression of B-type natriuretic peptide (BNP) and components of the renin-angiotensinogen and endothelin (ET)-1 systems. Our aim was to evaluate perinatal myocardium expression of these genes associated with ventricular pressure overload in a nitrofen-induced CDH rat model. METHODS: In the nitrofen-induced CDH rat model, fetuses from dated pregnant Sprague-Dawley rats at 15.5, 17.5, 19.5 and 21.5 days postcoitum as well as newborn pups were assigned to 3 experimental groups: control, nitrofen (exposed to nitrofen, without CDH), and CDH (exposed to nitrofen, with CDH). Myocardial samples collected from the RV and left ventricle (LV) were processed for quantification of messenger RNA (mRNA) of BNP, angiotensinogen, and ET-1. RESULTS: The perinatal expression of BNP, angiotensinogen, and ET-1 mRNA in the RV and LV of the control group revealed daily changes. During gestation, the expression of BNP and angiotensinogen mRNA underwent significant oscillation compared with control in both nitrofen-exposed fetuses, although we cannot identify significant differences between the nitrofen and CDH groups. After birth, we found a significant increasing expression of all studied genes only in the RV of CDH pups. CONCLUSIONS: Perinatal myocardial quantification of BNP, angiotensinogen, and ET-1 mRNA levels suggests that both nitrofen-exposed and control pups revealed prenatal variations of expression of the studied genes. Moreover, CDH is associated with significant molecular alterations only in the RV after birth.
Authors: Aline Vuckovic; Susanne Herber-Jonat; Andreas W Flemmer; Brigitte Strizek; Alexander C Engels; Jacques C Jani Journal: Am J Physiol Lung Cell Mol Physiol Date: 2016-02-12 Impact factor: 5.464
Authors: Matthew J Egan; Nazia Husain; Jack R Stines; Nasser Moiduddin; Melanie A Stein; Leif D Nelin; Clifford L Cua Journal: World J Pediatr Date: 2012-11-15 Impact factor: 2.764