Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
J Histochem Cytochem. 2011 Aug;59(8):761-8. doi: 10.1369/0022155411411712. Epub 2011 May 23.
The authors' previous studies have indicated that angiotensin(Ang)-(1-7) protects the heart against reperfusion arrhythmias. The aim of this study was to determine whether a functional angiotensin-converting enzyme2 (ACE2)/Ang-(1-7)/Mas receptor axis is present in the sinoatrial node (SAN) of Wistar rats. SAN cells were identified by Masson's trichrome staining, HCN4 expression, and lack of connexin43 expression. Immunohistochemistry technique was used to detect the expression of ACE2, Ang-(1-7), and Mas in the SAN. To evaluate the role of this axis in the SAN function, atrial tachyarrhythmias (ATs) were induced in isolated rat atria perfused with Krebs-Ringer solution (KRS) alone (control) or KRS containing Ang-(1-7). The specific Mas antagonist, A-779, was used to evaluate the role of Mas in the Ang-(1-7) effects. The findings showed that all components of the ACE2/Ang-(1-7)/Mas branch are present in the SAN of rats. Importantly, it was found that this axis is functional because perfusion of atria with Ang-(1-7) significantly reduced the duration of ATs. Additionally, this anti-arrhythmogenic effect was attenuated by A-779. No significant changes were observed in heart rate, contractile tension, or ±dT/dt. These observations demonstrate that the ACE2/Ang-(1-7)/Mas axis is expressed in SAN cells of rats. They provide the morphological support to the anti-arrhythmogenic effect of Ang-(1-7).
作者先前的研究表明血管紧张素(Ang)-(1-7)可保护心脏免受再灌注心律失常的影响。本研究旨在确定功能性血管紧张素转换酶 2(ACE2)/Ang-(1-7)/Mas 受体轴是否存在于 Wistar 大鼠的窦房结(SAN)中。通过 Masson 三色染色、HCN4 表达和缺乏连接蛋白 43 表达来鉴定 SAN 细胞。免疫组织化学技术用于检测 SAN 中 ACE2、Ang-(1-7)和 Mas 的表达。为了评估该轴在 SAN 功能中的作用,在单独用 Krebs-Ringer 溶液(KRS)(对照)或含有 Ang-(1-7)的 KRS 灌注的分离大鼠心房中诱导房性心动过速(ATs)。使用特定的 Mas 拮抗剂 A-779 来评估 Mas 在 Ang-(1-7)作用中的作用。研究结果表明,ACE2/Ang-(1-7)/Mas 分支的所有成分都存在于大鼠的 SAN 中。重要的是,发现该轴是功能性的,因为用 Ang-(1-7)灌注心房可显著缩短 ATs 的持续时间。此外,A-779 减弱了这种抗心律失常作用。心率、收缩张力或±dT/dt 没有观察到明显变化。这些观察结果表明 ACE2/Ang-(1-7)/Mas 轴在大鼠的 SAN 细胞中表达。它们为 Ang-(1-7)的抗心律失常作用提供了形态学支持。