Renin–angiotensin system: Basic and clinical aspects—A general perspective

Vargas, Rafael; Millán, Jesús; Bonilla, Esperanza Fajardo

doi:10.1016/j.endien.2022.01.005

Cited by 22 publications

(7 citation statements)

References 67 publications

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“…However, the newly discovered ACE2/Ang-(1–7)/Mas axis within the RAS system is crucial for maintaining nervous system homeostasis by mediating vasodilation, anti-inflammatory effects, and anti-apoptotic actions. This pathway effectively counteracts the effects of the ACE/Ang-II/AT1 axis [ 15 – 17 ]. Thus, targeting the local brain RAS system is a promising approach to treating CNS injury.…”

Section: Introductionmentioning

confidence: 99%

Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice

Deng,

Ren,

Chen

et al. 2024

J Neuroinflammation

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Background Intracerebral hemorrhage (ICH) is a devastating neurological disease causing severe sensorimotor dysfunction and cognitive decline, yet there is no effective treatment strategy to alleviate outcomes of these patients. The Mas axis-mediated neuroprotection is involved in the pathology of various neurological diseases, however, the role of the Mas receptor in the setting of ICH remains to be elucidated. Methods C57BL/6 mice were used to establish the ICH model by injection of collagenase into mice striatum. The Mas receptor agonist AVE0991 was administered intranasally (0.9 mg/kg) after ICH. Using a combination of behavioral tests, Western blots, immunofluorescence staining, hematoma volume, brain edema, quantitative-PCR, TUNEL staining, Fluoro-Jade C staining, Nissl staining, and pharmacological methods, we examined the impact of intranasal application of AVE0991 on hematoma absorption and neurological outcomes following ICH and investigated the underlying mechanism. Results Mas receptor was found to be significantly expressed in activated microglia/macrophages, and the peak expression of Mas receptor in microglia/macrophages was observed at approximately 3–5 days, followed by a subsequent decline. Activation of Mas by AVE0991 post-treatment promoted hematoma absorption, reduced brain edema, and improved both short- and long-term neurological functions in ICH mice. Moreover, AVE0991 treatment effectively attenuated neuronal apoptosis, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines in perihematomal areas after ICH. Mechanistically, AVE0991 post-treatment significantly promoted the transformation of microglia/macrophages towards an anti-inflammatory, phagocytic, and reparative phenotype, and this functional phenotypic transition of microglia/macrophages by Mas activation was abolished by both Mas inhibitor A779 and Nrf2 inhibitor ML385. Furthermore, hematoma clearance and neuroprotective effects of AVE0991 treatment were reversed after microglia depletion in ICH. Conclusions Mas activation can promote hematoma absorption, ameliorate neurological deficits, alleviate neuron apoptosis, reduced neuroinflammation, and regulate the function and phenotype of microglia/macrophages via Akt/Nrf2 signaling pathway after ICH. Thus, intranasal application of Mas agonist ACE0991 may provide promising strategy for clinical treatment of ICH patients.

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Section: Introductionmentioning

confidence: 99%

Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice

Deng,

Ren,

Chen

et al. 2024

J Neuroinflammation

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“…However, its complexity and involvement in other systemic pathways were initially underappreciated. Over time, our understanding of RAS has evolved and it is now implicated in the pathogenesis of numerous acute and chronic conditions including COVID-19, renal dysfunction, diabetes mellitus, hypertension, and cardiac disease, including heart failure and myocardial infarction [ 2 , 3 ]. RAS has traditionally been considered to be upregulated in these conditions, promoting inflammation and vasoconstriction through angiotensin II (AngII) and its principal receptor, angiotensin type I receptor (AT1R) [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

The Renin–Angiotensin System in Liver Disease

McGrath,

Wentworth

2024

IJMS

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The renin–angiotensin system (RAS) is a complex homeostatic entity with multiorgan systemic and local effects. Traditionally, RAS works in conjunction with the kidney to control effective arterial circulation, systemic vascular resistance, and electrolyte balance. However, chronic hepatic injury and resulting splanchnic dilation may disrupt this delicate balance. The role of RAS in liver disease, however, is even more extensive, modulating hepatic fibrosis and portal hypertension. Recognition of an alternative RAS pathway in the past few decades has changed our understanding of RAS in liver disease, and the concept of opposing vs. “rebalanced” forces is an ongoing focus of research. Whether RAS inhibition is beneficial in patients with chronic liver disease appears to be context-dependent, but further study is needed to optimize clinical management and reduce organ-specific morbidity and mortality. This review presents the current understanding of RAS in liver disease, acknowledges areas of uncertainty, and describes potential areas of future investigation.

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“…The renin-angiotensin system (RAS), which acts mainly through renin, angiotensin I (Ang I), angiotensin II (Ang II), angiotensin-converting enzyme (ACE) and aldosterone (ALD), is recognized as a circulating hormone system [10,11]. However, in recent years, it has been shown that the main family members of the RAS are localized to testicular tissues [10,12,13].…”

Section: Introductionmentioning

confidence: 99%

Exogenous Nucleotides Ameliorate Age-Related Decline in Testosterone in Male Senescence-Accelerated Mouse Prone-8 (SAMP8) Mice by Modulating the Local Renin–Angiotensin System Antioxidant Pathway

Chen,

Liu,

Wei

et al. 2023

Nutrients

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In older men, an age-related decline in testosterone is closely associated with various adverse health outcomes. With the progression of aging, hyperactivation of the local renin–angiotensin system (RAS) and oxidative stress increase in the testis. The regulation of RAS antioxidants may be a target to delay testicular aging and maintain testosterone levels. Exogenous nucleotides (NTs) have anti-aging potential in several systems, but there are no studies of their effects on the reproductive system. In our study, we examined the effects of exogenous NTs on testosterone synthesis and explored possible mechanisms of action. Therefore, senescence-accelerated mouse prone-8 (SAMP8) mice and senescence-accelerated mouse resistant 1 (SAMR1) were used in the experiment, and they were randomly divided into an NTs free group (NTs-F), a normal control group (control), a low-dose NTs group (NTs-L), a middle-dose NTs (NTs-M), a high-dose NTs group (NTs-H) and SAMR1 groups, and the testis of the mice were collected for testing after 9 months of intervention. The results showed that exogenous NTs could increase the testicular organ index in mice during aging, and delayed the age-associated decline in testosterone levels in SAMP8 male mice, possibly by modulating the local RAS antioxidant pathway and reducing oxidative stress to protect the testis. The present study provides new research clues for the development of preventive and therapeutic strategies for related diseases.

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Renin–angiotensin system: Basic and clinical aspects—A general perspective

Cited by 22 publications

References 67 publications

Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice

Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice

The Renin–Angiotensin System in Liver Disease

Exogenous Nucleotides Ameliorate Age-Related Decline in Testosterone in Male Senescence-Accelerated Mouse Prone-8 (SAMP8) Mice by Modulating the Local Renin–Angiotensin System Antioxidant Pathway

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