Descrição
Antenatal stimulation of lung growth is a reasonable approach to treat congenital diaphragmatic hernia (CDH), a disease
characterized by pulmonary hypoplasia and hypertension. Several evidences from the literature demonstrated a possible involvement
of renin-angiotensin system (RAS) during fetal lung development. Thus, the expression pattern of renin, angiotensin-converting
enzyme, angiotensinogen, type 1 (AT1) and type 2 (AT2) receptors of angiotensin II (ANGII) was assessed by immunohistochemistry
throughout gestation, whereas the function of RAS in the fetal lung was evaluated using fetal rat lung explants. These
were morphometrically analyzed and intracellular pathway alterations assessed by Western blot. In nitrofen-induced CDH model,
pregnant rats were treated with saline or PD-123319. In pups, lung growth, protein/DNA ratio, radial saccular count, epithelial differentiation
and lung maturation, vascular morphometry, right ventricular hypertrophy and overload molecular markers, gasometry
and survival time were evaluated. Results demonstrated that all RAS components were constitutively expressed in the lung
during gestation and that ANGII had a stimulatory effect on lung branching, mediated by AT1 receptor, through p44/42 and Akt
phosphorylation. This stimulatory effect on lung growth was mimicked by AT2-antagonist (PD-123319) treatment. In vivo antenatal
PD-123319 treatment increased lung growth, ameliorated indirect parameters of pulmonary hypertension, improved lung function
and survival time in nonventilated CDH pups, without maternal or fetal deleterious effects. Therefore, this study demonstrated a
local and physiologically active RAS during lung morphogenesis. Moreover, selective inhibition of AT2 receptor is presented as a
putative antenatal therapy for CDH.
; Dias, Emanuel Carvalho 
