Angiotensin-converting enzyme 2 activator, DIZE in the basolateral amygdala attenuates the tachycardic response to acute stress by modulating glutamatergic tone

Carina Cunha Silva, Ana Maria Bernal Correa, Christopher Kushmerick, Neeru M. Sharma, Kaushik P. Patel, Jônathas Fernandes Queiroz de Almeida, Fabrício A. Moreira, Anderson José Ferreira, Marco Antônio Peliky Fontes

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number102076
JournalNeuropeptides
Volume83
DOIs
StatePublished - Oct 2020

Keywords

  • Angiotensin-converting enzyme 2
  • Cardiovascular diseases
  • Diminazene aceturate
  • Emotional stress
  • amygdala
  • renin angiotensin system

ASJC Scopus subject areas

  • Endocrinology
  • Neurology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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