Kangussu Lucas M, Almeida-Santos Ana Flávia, Moreira Fabrício A, Fontes Marco A P, Santos Robson A S, Aguiar Daniele C, Campagnole-Santos Maria José
Department of Physiology and Biophysics.
Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Behav Brain Res. 2017 Jul 28;331:193-198. doi: 10.1016/j.bbr.2017.05.026. Epub 2017 May 11.
Angiotensin-(1-7) [Ang-(1-7)], a counterregulatory peptide of the renin-angiotensin system (RAS), exerts its cardiovascular and renal functions through the G-protein-coupled receptor Mas. More recently, Ang-(1-7) has also been implicated in the control of emotional states related to fear and anxiety. Here, we tested the hypothesis that transgenic rats overexpressesing Ang-(1-7) (TGR) show reduced anxiety-like behavior in two distinct animals models, the Elevated Plus Maze (EPM) and Vogel Conflict Test (VCT). Sprague-Dawley rats (SDs) were used as controls. In addition, we also verified whether this phenotype depend on activation of the Mas receptor. In line with our hypothesis, TGR rats showed an increase in the percentage of time and entries in the open arms of the EPM. There was also an increase in the number of punished licks in VCT. These phenotypes were reversed by ICV injection of the Mas receptor antagonist, A779, but not by the AT and MrgD receptor antagonist, PD123319. These results suggest that chronic elevation of Ang-(1-7) levels results in a phenotype characterized by reduced anxiety-like behavior, possibly due to higher activation of the Mas receptor. Therefore, facilitation of the Ang-(1-7)/Mas receptor signaling may be further investigated as an additional strategy for the treatment of anxiety-related disorders.
血管紧张素 -（1 - 7）[Ang -（1 - 7）]是肾素 - 血管紧张素系统（RAS）的一种负调节肽，它通过G蛋白偶联受体Mas发挥其心血管和肾脏功能。最近，Ang -（1 - 7）也被认为与恐惧和焦虑相关的情绪状态控制有关。在此，我们测试了一个假设，即过表达Ang -（1 - 7）的转基因大鼠（TGR）在两种不同的动物模型，即高架十字迷宫（EPM）和Vogel冲突试验（VCT）中表现出焦虑样行为减少。Sprague - Dawley大鼠（SDs）用作对照。此外，我们还验证了这种表型是否依赖于Mas受体的激活。与我们的假设一致，TGR大鼠在EPM开放臂中的停留时间百分比和进入次数增加。VCT中受罚舔舐次数也增加。这些表型可通过脑室内注射Mas受体拮抗剂A779逆转，但不能通过AT和MrgD受体拮抗剂PD123319逆转。这些结果表明，Ang -（1 - 7）水平的慢性升高导致一种以焦虑样行为减少为特征的表型，这可能是由于Mas受体的更高激活所致。因此，作为治疗焦虑相关疾病的额外策略，可进一步研究促进Ang -（1 - 7）/Mas受体信号传导。
