The basolateral amygdala (BLA) is critical in the control of the sympathetic output during stress. Studies demonstrated the involvement of the renin-angiotensin system components in the BLA. Angiotensin-(1-7) [Ang-(1-7)], acting through Mas receptors, reduces stress effects. Considering that angiotensin-converting enzyme 2 (ACE2) is the principal enzyme for the production of Ang-(1-7), here we evaluate the cardiovascular reactivity to acute stress after administration of the ACE2 activator, diminazene aceturate (DIZE) into the BLA. We also tested whether systemic treatment with DIZE could modify synaptic activity in the BLA and its effect directly on the expression of the N-methyl-d-aspartate receptors (NMDARs) in NG108 neurons in-vitro. Administration of DIZE into the BLA (200 pmol/100 nL) attenuated the tachycardia to stress (ΔHR, bpm: vehicle = 103 ± 17 vs DIZE = 49 ± 7 p = 0.018); this effect was inhibited by Ang-(1-7) antagonist, A-779 (ΔHR, bpm: DIZE = 49 ± 7 vs A-779 + DIZE = 100 ± 15 p = 0.04). Systemic treatment with DIZE attenuated the excitatory synaptic activity in the BLA (Frequency (Hz): vehicle = 2.9 ± 0.4 vs. DIZE =1.8 ± 0.3 p < 0.04). NG108 cells treated with DIZE demonstrated decreased expression of l subunit NMDAR-NR1 (NR1 expression (a.u): control = 0.534 ± 0.0593 vs. DIZE = 0.254 ± 0.0260) of NMDAR and increases of Mas receptors expression. These data demonstrate that DIZE attenuates the tachycardia evoked by acute stress. This effect results from a central action in the BLA involving activation of Mas receptors. The ACE2 activation via DIZE treatment attenuated the frequency of excitatory synaptic activity in the basolateral amygdala and this effect can be related with the decreases of the NMDAR-NR1 receptor expression.

中文翻译：

---

基底外侧杏仁核中的血管紧张素转换酶 2 激活剂 DIZE 通过调节谷氨酸能张力减弱对急性应激的心动过速反应

基底外侧杏仁核 (BLA) 在压力期间控制交感神经输出至关重要。研究表明肾素-血管紧张素系统成分参与 BLA。血管紧张素-(1-7) [Ang-(1-7)] 通过 Mas 受体起作用，可减少压力影响。考虑到血管紧张素转换酶 2 (ACE2) 是产生 Ang-(1-7) 的主要酶，我们在这里评估了将 ACE2 激活剂乙酰二胺 (DIZE) 注入 BLA 后对急性应激的心血管反应性. 我们还测试了 DIZE 全身治疗是否可以改变 BLA 中的突触活动及其对体外 NG108 神经元中 N-甲基-d-天冬氨酸受体 (NMDAR) 表达的直接影响。将 DIZE 注入 BLA (200 pmol/100 nL) 可减轻心动过速对压力的影响 (ΔHR, bpm: 车辆 = 103 ± 17 与 DIZE = 49 ± 7 p = 0.018）；这种作用被 Ang-(1-7) 拮抗剂 A-779 抑制（ΔHR，bpm：DIZE = 49 ± 7 vs A-779 + DIZE = 100 ± 15 p = 0.04）。用 DIZE 进行全身治疗减弱了 BLA 中的兴奋性突触活动（频率 (Hz)：载体 = 2.9 ± 0.4 与 DIZE =1.8 ± 0.3 p < 0.04）。用 DIZE 处理的 NG108 细胞表明 NMDAR 的 l 亚基 NMDAR-NR1 的表达降低（NR1 表达（au）：对照 = 0.534 ± 0.0593 vs. DIZE = 0.254 ± 0.0260），并且 Mas 受体表达增加。这些数据表明 DIZE 可减轻急性应激引起的心动过速。这种效应源于 BLA 中涉及激活 Mas 受体的中枢作用。