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Altered expression of angiotensin II receptor subtypes and transforming growth factor-β in the heart of nitrofen-induced diaphragmatic hernia in rats

Pediatric Surgery International volume 21, pages 148–152 (2005)Cite this article

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-β1(TGF-β1) 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-β1 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-β1. Levels of mRNA were expressed as a ratio of the band density divided by that of β-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-β1 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-β1 mRNA in the hypoplastic heart suggests that the downregulation of RAS may be involved in the pathogenesis of cardiac hypoplasia in nitrofen-induced CDH.

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  1. Children’s Research Center, Our Lady’s Hospital for Sick Children, University College, Crumlin, Dublin, 12, Ireland

    Honami Teramoto, Masato Shinkai & Prem Puri

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  1. Honami Teramoto
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  2. Masato Shinkai
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  3. Prem Puri
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Correspondence to Prem Puri.

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Teramoto, H., Shinkai, M. & Puri, P. Altered expression of angiotensin II receptor subtypes and transforming growth factor-β in the heart of nitrofen-induced diaphragmatic hernia in rats. Ped Surgery Int 21, 148–152 (2005). https://doi.org/10.1007/s00383-004-1311-7

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  • DOI: https://doi.org/10.1007/s00383-004-1311-7

Keywords

  • Congenital diaphragmatic hernia
  • Hypoplastic heart
  • Angiotensin II
  • Transforming growth factor-β