Central Administration of Angiotensin-(1-7) Improves Vasopressin Impairment and Hypotensive Response in Experimental Endotoxemia

Author(s)

Passaglia, Patricia ^[1] ; de Lima Faim, Felipe ^[1] ; Batalhao, Marcelo Eduardo ^[2] ; Stabile, Angelita Maria ^[2] ; Bendhack, Lusiane Maria ^[3] ; Antunes-Rodrigues, Jose ^[1] ; Lacchini, Riccardo ^[4] ; Capellari Carnio, Evelin ^[2]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Physiol, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Coll Nursing, Dept Gen & Specialized Nursing, BR-14040902 Ribeirao Preto, SP - Brazil

^[3] Univ Ribeirao Preto, Fac Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, BR-14040903 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Coll Nursing, Dept Psychiat Nursing & Human Sci, BR-14040902 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: CELLS; v. 10, n. 1 JAN 2021.
• Web of Science Citations: 0

Abstract

Angiotensin-(1-7) {[}Ang-(1-7)]/Mas receptor is a counter-regulatory axis that counteracts detrimental renin-angiotensin system (RAS) effects, especially regarding systemic inflammation, vasopressin (AVP) release, and hypothalamic-pituitary-adrenal (HPA) activation. However, it is not completely understood whether this system may control centrally or systemically the late phase of systemic inflammation. Thus, the aim of this study was to determine whether intracerebroventricular (i.c.v.) administration of Ang-(1-7) can modulate systemic inflammation through the activation of humoral pathways in late phase of endotoxemia. Endotoxemia was induced by systemic injection of lipopolysaccharide (LPS) (1.5 mg/kg, i.v.) in Wistar rats. Ang-(1-7) (0.3 nmol in 2 mu L) promoted the release of AVP and attenuated interleukin-6 (IL-6) and nitric oxide (NO) levels but increased interleukin-10 (IL-10) in the serum of the endotoxemic rats. The central administration of Mas receptor antagonist A779 (3 nmol in 2 mu L, i.c.v.) abolished these anti-inflammatory effects in endotoxemic rats. Furthermore, Ang-(1-7) applied centrally restored mean arterial blood pressure (MABP) without affecting heart rate (HR) and prevented vascular hyporesponsiveness to norepinephrine (NE) and AVP in animals that received LPS. Together, our results indicate that Ang-(1-7) applied centrally promotes a systemic anti-inflammatory effect through the central Mas receptor and activation of the humoral pathway mediated by AVP. (AU)

• FAPESP's process: 14/22477-6 - Participation of angiotensin-(1-7) in the regulation of synthesis and release of vasopressin during endotoxemia
• Grantee: Patrícia Passaglia
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/20343-4 - Antiinflammatory cholinergic pathway: the role of neuroimmunomodulation in the control of inflammatory response
• Grantee: Alexandre Kanashiro
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 15/09857-7 - Central effect of angiotensin (1-7) on the vasopressin release during endotoxemic shock.
• Grantee: Evelin Capellari Cárnio
• Support Opportunities: Regular Research Grants