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

Autor(es)

Passaglia, Patricia ^[1] ; Faim, Felipe de Lima ^[1] ; Batalhao, Marcelo Eduardo ^[2] ; Bendhack, Lusiane Maria ^[3] ; Antunes-Rodrigues, Jose ^[1] ; Ulloa, Luis ^[4] ; Kanashiro, Alexandre ^[5] ; Carnio, Evelin Capellari ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Physiol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Coll Nursing, Dept Gen & Specialized Nursing Ribeirao Preto, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, Ribeirao Preto, SP - Brazil

^[4] Duke Univ, Med Ctr, Dept Anesthesiol, Ctr Perioperat Organ Protect, Durham, NC 27710 - USA

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BRAIN BEHAVIOR AND IMMUNITY; v. 88, p. 606-618, AUG 2020.
• Citações Web of Science: 1

Resumo

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 mu L) 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 mu L) 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. (AU)

• Processo FAPESP: 11/20343-4 - Via colinérgica anti-inflamatória: o papel da neuroimunomodulação no controle da resposta inflamatória
• Beneficiário: Alexandre Kanashiro
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 15/09857-7 - Ação central de angiotensina (1-7) sobre a liberação de vasopressina durante o choque endotoxêmico.
• Beneficiário: Evelin Capellari Cárnio
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/22477-6 - Participação da angiotensina-(1-7) na regulação da síntese e liberação de vasopressina durante a endotoxemia
• Beneficiário: Patrícia Passaglia
• Modalidade de apoio: Bolsas no Brasil - Doutorado