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

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 µL) 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 µL, 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.

Insight Into Regulatory T Cells in Sepsis-Associated Encephalopathy

“…The immuno-inflammatory signals affect different regions of the brain, mainly through humoral and neural pathways, which mostly involve damage of the BBB and activation of vagal afferent fibers, respectively ( 4 , 5 , 8 , 59 ). At the same time, CNS dysfunction may be an important cause of neuroendocrine-immune network breakdown, as well as a potential therapeutic target (such as cholinergic anti-inflammatory pathway, humoral pathway mediated by vasopressin, and reconstruction of the HPA axis) for sepsis-induced immunosuppression or endocrine dysfunction ( 19 , 63 , 118 ). The dysregulation of cholinergic and inflammatory systems are the main pathophysiologic mechanisms regulating other brain injuries (such as hepatic encephalopathy and ischemic encephalopathy).…”

Arginine vasopressin and pathophysiology of COVID-19: An innovative perspective

“…Elevated AngII stimulates hypothalamus to release of AVP, which causes hyponatremia and release of more inflammatory cytokines [69] . However, central administration of Ang1-7 inhibits release of AVP from hypothalamus via anti-inflammatory effect [70] . Furthermore, high AVP in SARS-CoV-2 infection might be due to AngII-induced hypothalamic activation or due to AngII-induced immune cells activation that also release AVP.…”