title: Altered expression of angiotensin II receptor subtypes and transforming growth factor-beta in the heart of nitrofen-induced diaphragmatic hernia in rats.
abstract: The renin-angitensin system (RAS) plays an important role as a growth factor in cardiac development. Angiotensin converting enzyme is involved in converting angiotensin I to angiotensin II (Ag-II). The effects of Ag-II are mediated by two primary receptors, type 1 (AT1) and type 2 (AT2). Ag-II stimulates transforming growth factor-beta1(TGF-beta1) and acts as a potent stimulant of myocyte growth and fetal contractile protein gene transcription. The aim of this study was to determine the expression of Ag-II receptor subtypes and TGF-beta1 in the hypoplastic heart of nitrofen-induced congenital diaphragmatic hernia (CDH). CDH was induced in pregnant rats following administration of 100 mg nitrofen on day 9.5. The fetuses were divided into three groups: normal controls (n=16), nitrofen-treated without CDH (n=16), and nitrofen-induced CDH (n=16). Reverse transcriptase-polymerase chain reaction was performed to evaluate mRNA expression of AT1, AT2, and TGF-beta1. Levels of mRNA were expressed as a ratio of the band density divided by that of beta-actin. AT1 and AT2 mRNA expressions were significantly decreased in CDH heart compared with controls (0.43+/-0.33 vs. 1.0+/-0.48 and 0.62+/-0.23 vs. 1.4+/-0.43, respectively). TGF-beta1 mRNA expressions were also significantly decreased in CDH heart compared with controls (0.38+/-0.17 vs. 0.72+/-0.26). No significant difference was found between the hearts of controls and nitrofen-treated rats without CDH. The decreased expression of AT1, AT2, and TGF-beta1 mRNA in the hypoplastic heart suggests that the downregulation of RAS may be involved in the pathogenesis of cardiac hypoplasia in nitrofen-induced CDH.
authors.affiliation: Children's Research Center, Our Lady's Hospital for Sick Children, University College, Crumlin, Dublin 12, Ireland.
authors.forename: Honami
authors.initials: H
authors.lastname: Teramoto
authors.forename: Masato
authors.initials: M
authors.lastname: Shinkai
authors.forename: Prem
authors.initials: P
authors.lastname: Puri
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006321:Heart / Q000196:embryology; D006540:Herbicides / Q000633:toxicity; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000378:metabolism*; D018811:Maternal Exposure / Q000009:adverse effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010647:Phenyl Ethers / Q000633:toxicity; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics* / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
chemical_list: D006540:Herbicides; D010647:Phenyl Ethers; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D016212:Transforming Growth Factor beta; C007350:nitrofen