期刊
NEUROPEPTIDES
卷 83, 期 -, 页码 -出版社
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.npep.2020.102076
关键词
Emotional stress; renin angiotensin system; Angiotensin-converting enzyme 2; Diminazene aceturate; Cardiovascular diseases; amygdala
资金
- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais [FAPEMIG CBB-APQ-01463-15]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico do Brazil (CNPq) [PQ30388/2017-3]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, CAPES, Brazil
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)], acing 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 (MR, bpm: vehicle = 103 +/- 17 vs DIZE = 49 +/- 7 p = 0.018); this effect was inhibited by Ang-(1-7) antagonist, A-779 (Delta HR, 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 1 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.
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