Central angiotensin-(1–7) attenuates systemic inflammation via activation of sympathetic signaling in endotoxemic rats

Patrícia Passaglia, Felipe de Lima Faim, Marcelo Eduardo Batalhão, Lusiane Maria Bendhack, José Antunes-Rodrigues, Luis Ulloa, Alexandre Kanashiro, Evelin Capellari Carnio

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Angiotensin-(1–7) [Ang-(1–7)] is an angiotensin-derived neuropeptide with potential anti-hypertensive and anti-inflammatory properties. However, a possible action of Ang-(1–7) in neuroimmune interactions to regulate inflammatory response has not been explored. Thus, the aim of this study was to determine whether the intracerebroventricular (i.c.v.) administration of Ang-(1–7) can modulate systemic inflammation via sympathetic efferent circuits. Wistar male rats received systemic administration of lipopolysaccharide (LPS) (1.5 mg/Kg). Ang-(1–7) (0.3 nmol in 2 µL) promoted the release of splenic norepinephrine and attenuated tumor necrosis factor (TNF) and nitric oxide (NO), but increased interleukin-10 (IL-10), levels in the serum, spleen, and liver in endotoxemic rats. Furthermore, 6-hydroxydopamine-induced chemical sympathectomy (100 mg/Kg, intravenous) or i.c.v. administration of Mas receptor antagonist A779 (3 nmol in 2 µL) abolished the anti-inflammatory effects of central Ang-(1–7) injection. Moreover, this treatment did not alter the plasmatic LPS-induced corticosterone and vasopressin. The administration of Ang-(1–7) reverted the low resistance in response to catecholamines of rings of thoracic aorta isolated from endotoxemic rats, treated or not, with this peptide by a mechanism dependent on the regulation of NO released from perivascular adipose tissue. Together, our results indicate that Ang-(1–7) regulates systemic inflammation and vascular hyporesponsiveness in endotoxemia via activation of a central Mas receptors/sympathetic circuits/norepinephrine axis and provide novel mechanistic insights into the anti-inflammatory Ang-(1–7) properties.

Original languageEnglish (US)
Pages (from-to)606-618
Number of pages13
JournalBrain, Behavior, and Immunity
Volume88
DOIs
StatePublished - Aug 2020

All Science Journal Classification (ASJC) codes

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Keywords

  • Angiotensin-(1–7)
  • Hypotension
  • Inflammatory reflex
  • Lipopolysaccharide
  • Neuroimmunomodulation
  • Sympathetic nervous system
  • Vascular reactivity

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