O Seu Saber Ocupa um Lugar! DSpace

Repositório Comum >
HB - Hospital de Braga >
HB - Cirurgia Pediátrica >
HB - CIR PED - Artigos >

Please use this identifier to cite or link to this item: http://comum.rcaap.pt/handle/123456789/2804

Título: Local fetal lung renin-angiotensin system as a target to treat congenital diaphragmatic hernia
Autor: Nogueira-Silva, C
Carvalho-Dias, C
Piairo, P
Nunes, S
Baptista, MJ
Moura, RS
Correia-Pinto, J
Palavras-chave: Feto
Hérnia Diafragmática
Sistema Renina-Angiotensina
Issue Date: 2012
Citação: Mol Med. 2012;18(1):231-43
Resumo: 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 immunohisto-chemistry 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.
Arbitragem científica: yes
URI: http://comum.rcaap.pt/handle/123456789/2804
Appears in Collections:HB - CIR PED - Artigos
HB - GIN OB - Artigos

Files in This Item:

File Description SizeFormat
Local fetal lung renin-angiotensin system as a target to treat congenital diaphragmatic hernia.pdf3,99 MBAdobe PDFView/Open
Statistics
FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpaceOrkut
Formato BibTex mendeley Endnote Logotipo do DeGóis 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

© 2014 - REPOSITÓRIO COMUM - Comentários - Statistics
Promotores do RCAAP   Financiadores do RCAAP

Fundação para a Ciência e a Tecnologia Universidade do Minho   Governo Português Ministério da Educação e Ciência PO Sociedade do Conhecimento (POSC) Portal oficial da União Europeia