Price R L, Carver W, Simpson D G, Fu L, Zhao J, Borg T K, Terracio L
Department of Developmental Biology and Anatomy, School of Medicine, University of South Carolina, Columbia 29208, USA.
Dev Biol. 1997 Dec 15;192(2):572-84. doi: 10.1006/dbio.1997.8764.
The role of angiotensin II (Ang II) in the early embryonic development of the heart has not been examined. We have used RT-PCR to identify mRNA for angiotensinogen, angiotensin-converting enzyme, and the Ang II AT1 and AT2 receptors in embryonic day 10.25 Sprague-Dawley rats, and have used confocal microscopy to localize the AT1 receptor to the greater curvature of the developing ventricle in these animals at embryonic days (ED) 9.25 and 10.25. The antibodies used in immunolocalization studies did not distinguish between the AT1a and AT1b receptor subtypes. In whole embryo culture, Ang II added to the culture media resulted in increased ventricular growth and myocyte hypertrophy when treated embryos were compared to cultured littermate controls. Use of Losartan and PD123,319 to block the Ang II AT1 and AT2 receptors resulted in reduced ventricular development and cardiac dilation when compared to control and Ang II-treated embryos. Addition of Ang II and PD123,319 to the culture media also resulted in cardiac loop inversions which may be associated with disruption of normal myofibrillar development. These results clearly indicate an important role for Ang II in the early embryonic development of the heart.
血管紧张素II（Ang II）在心脏早期胚胎发育中的作用尚未得到研究。我们运用逆转录聚合酶链反应（RT-PCR），在胚胎第10.25天的斯普拉格-道利大鼠中鉴定血管紧张素原、血管紧张素转换酶以及Ang II的AT1和AT2受体的信使核糖核酸（mRNA），并利用共聚焦显微镜在胚胎第9.25天和10.25天，将AT1受体定位到这些动物发育中的心室大弯处。免疫定位研究中使用的抗体无法区分AT1a和AT1b受体亚型。在全胚胎培养中，与培养的同窝对照相比，向培养基中添加Ang II会使处理后的胚胎心室生长增加且心肌细胞肥大。与对照和Ang II处理的胚胎相比，使用氯沙坦和PD123,319阻断Ang II的AT1和AT2受体，会导致心室发育减少和心脏扩张。向培养基中添加Ang II和PD123,319还会导致心脏环反转，这可能与正常肌原纤维发育的破坏有关。这些结果清楚地表明Ang II在心脏早期胚胎发育中起重要作用。
