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

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

doi:10.1016/j.bbi.2020.04.059

Cited by 8 publications

(6 citation statements)

References 75 publications

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“…The anti-inflammatory action of Ang1-7 was later confirmed in LPS-treated peritoneal macrophages (65) and in a polymicrobial sepsis rat model (66). Very recent results in an endotoxemia rat model show systemic antiinflammatory action of Ang1-7 that is mediated by the MasR (67).…”

Section: Ras Gpcrs the Blind Point In Sars Researchmentioning

confidence: 86%

SARS-CoV-2 as a Factor to Disbalance the Renin–Angiotensin System: A Suspect in the Case of Exacerbated IL-6 Production

Franco

Rivas‐Santisteban

Serrano-Marín

et al. 2020

The Journal of Immunology

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Fever in infections correlates with inflammation, macrophage infiltration into the affected organ, macrophage activation, and release of cytokines involved in immune response, hematopoiesis, and homeostatic processes. Angiotensin-converting enzyme 2 (ACE2) is the canonical cell surface receptor for SARS-CoV-2. ACE2 together with angiotensin receptor types 1 and 2 and ACE2 are components of the renin–angiotensin system (RAS). Exacerbated production of cytokines, mainly IL-6, points to macrophages as key to understand differential COVID-19 severity. SARS-CoV-2 may modulate macrophage-mediated inflammation events by altering the balance between angiotensin II, which activates angiotensin receptor types 1 and 2, and angiotensin 1–7 and alamandine, which activate MAS proto-oncogene and MAS-related D receptors, respectively. In addition to macrophages, lung cells express RAS components; also, some lung cells are able to produce IL-6. Addressing how SARS-CoV-2 unbalances RAS functionality via ACE2 will help design therapies to attenuate a COVID-19–related cytokine storm.

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Section: Ras Gpcrs the Blind Point In Sars Researchmentioning

confidence: 86%

SARS-CoV-2 as a Factor to Disbalance the Renin–Angiotensin System: A Suspect in the Case of Exacerbated IL-6 Production

Franco

Rivas‐Santisteban

Serrano-Marín

et al. 2020

The Journal of Immunology

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“…However, we cannot exclude the possibility that other neuroimmune routes participate in Ang-(1-7) anti-inflammatory effects in our experimental model. Our group recently demonstrated that in early stage of endotoxemia, Ang-(1-7) elicits anti-inflammatory effects through the activation of a neuroimmune pathway involving central activation of Mas receptors and subsequent sympathetic autonomic signaling [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…During endotoxemia, the vascular reactivity and endothelial barrier function are impaired, and this contributes to the hypotensive response [ 21 ]. In the vascular endothelium, LPS can cause synthesis and release of relatively high amounts of pro-inflammatory cytokines, which in turn produces relaxation of vascular smooth muscle tone resulting in hypotension and reduction of vasoconstrictor response to catecholamines [ 2 , 3 ].…”

Section: Discussionmentioning

confidence: 99%

“…Control animals were injected with the same volume of saline through the same routes. The doses of Ang-(1-7), A779, and LPS used were based on previous studies from our group [ 21 , 27 ]. Thus, the rats were divided into eight experimental groups according to analysis: (1) Saline (i.c.v.)…”

Section: Methodsmentioning

confidence: 99%

“…In addition to neuroendocrine actions, the activation of Ang-(1-7)/Mas receptor axis attenuates inflammation in several experimental models, including polymicrobial sepsis and cerebral ischemia [ 18 , 19 , 20 ]. In our most recent study, it has been shown that central administration of Ang-(1-7) prevented LPS-induced vascular hyporesponsiveness and hypotension due to an anti-inflammatory effect via activation of sympathetic signaling during the initial phase of endotoxemia [ 21 ]. However, the central mechanisms of Ang-(1-7) to control systemic inflammation in the late phase of endotoxemia are not well known.…”

Section: Introductionmentioning

confidence: 99%

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

Passaglia

Faim

Batalhão

et al. 2021

Cells

Self Cite

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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.

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Gestationally administered RAS modulators reprogram endotoxic cardiovascular and inflammatory profiles in adult male offspring of preeclamptic rats

Abuiessa,

Helmy,

El-Gowelli

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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

Cited by 8 publications

References 75 publications

SARS-CoV-2 as a Factor to Disbalance the Renin–Angiotensin System: A Suspect in the Case of Exacerbated IL-6 Production

SARS-CoV-2 as a Factor to Disbalance the Renin–Angiotensin System: A Suspect in the Case of Exacerbated IL-6 Production

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

Gestationally administered RAS modulators reprogram endotoxic cardiovascular and inflammatory profiles in adult male offspring of preeclamptic rats

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