Involvement of the Renin-Angiotensin System in Stress: State of the Art and Research Perspectives

2021 ◽  
Vol 19 ◽  
Author(s):  
Bernardo H. M. Correa ◽  
Luca Becari ◽  
Marco Antônio Peliky Fontes ◽  
Ana Cristina Simões-e-Silva ◽  
Lucas M. Kangussu
Keyword(s):  
Current Knowledge ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Post Traumatic Stress ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Canonical Systems ◽  
Renin Angiotensin ◽  
Research Perspectives ◽  
Air Jet

: Along with other canonical systems, the renin-angiotensin system (RAS) has shown essential roles in stress. This system is a complex regulatory proteolytic cascade composed of various enzymes, peptides, and receptors. Besides the classical (ACE/Ang II/AT 1 receptor) and the counter-regulatory (ACE2/Ang-(1-7)/Mas receptor) RAS axes, evidence indicates that non-classical components, including Ang III, Ang IV, AT 2, and AT 4, can also be involved in stress. Objective and methods: This comprehensive review summarizes the current knowledge on the participation of RAS components in different adverse environmental stimuli stressors, including air-jet stress, cage switch stress, restraint stress, chronic unpredictable stress, neonatal isolation stress, and post-traumatic stress disorder. Results and conclusion: In general, activating the classical RAS axis potentiates stress-related cardiovascular, endocrine, and behavioral responses, while the stimulation of the counter-regulatory axis attenuates these effects. Pharmacological modulation in both axes is optimistic, offering promising perspectives for stress-related disorders treatment. In this regard, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are potential candidates already available because they block the classical axis, activate the counter-regulatory axis, and are safe and efficient drugs.

HFrEF pharmacological treatment: ACEIs and/or ARBs

ESC CardioMed ◽  
2018 ◽  
pp. 1844-1848
Author(s):  
Marc A. Pfeffer
Keyword(s):  
Heart Failure ◽  
Angiotensin Receptor Blockers ◽  
Antihypertensive Agents ◽  
Drug Effects ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Reduced Ejection Fraction

Several classes of inhibitors of the renin–angiotensin system were developed as antihypertensive agents. Following the early observations of favourable haemodynamic effects of angiotensin-converting enzyme inhibitors (ACEIs) in patients with congestive heart failure, a series of major randomized outcome trials demonstrated morbidity and mortality benefits of these agents across the spectrum of patients with heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor blockers (ARBs) were then also shown to have similar benefits with a suggestion of some incremental improvements when used together. However, in the trials that randomized patients to a proven dose of an ACEI plus either placebo or an ARB, the combination of the two inhibitors of the renin–angiotensin system resulted in more adverse drug effects without a meaningful improvement in clinical outcomes. This chapter reviews the fundamental underpinnings for use of either an ACEI or ARB to improve prognosis of patients with HFrEF.

Use of Renin-Angiotensin System Antagonists in Patients with Hypertension and COVID-19 Infection: A Rapid Review and Meta-analysis

2020 ◽  
Vol 54 ◽  
Author(s):  
Rowena Natividad S. Flores-Genuino ◽  
Charissa Mia Salud-Gnilo ◽  
Evelyn Osio-Salido
Keyword(s):  
Heart Failure ◽  
Angiotensin Receptor Blockers ◽  
Severe Disease ◽  
Renin Angiotensin System ◽  
Rapid Review ◽  
Insufficient Evidence ◽  
Converting Enzyme Inhibitors ◽  
Cross Sectional ◽  
Angiotensin System ◽  
Renin Angiotensin

KEY FINDINGSAmong patients with confirmed COVID-19 infection and hypertension, there is insufficient evidence that RASantagonists are associated with mortality or severe COVID-19 disease.• There is uncertainty with regards to the safe use of renin-angiotensin system (RAS) antagonists, such asangiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), for COVID-19 patientswith hypertension and other comorbidities (heart failure, chronic kidney disease) because of two possiblecontradictory mechanisms 1) upregulation of ACE2 receptors that may facilitate the virus entry into the lung.and 2) control of unabated angiotensin II levels reducing acute lung injury.• Based on very low-quality retrospective cohort studies, there is insufficient evidence that RAS antagonists areassociated with increased mortality (6 studies) or severe disease (10 studies) among patients with confirmedCOVID-19 infection and hypertension.• There are 36 ongoing studies (21 RCTs, 1 single-arm trial, 4 prospective cohorts, 4 retrospective cohorts, 4 casecontrol, and 2 cross-sectional) on this topic.• The European Society of Cardiology (ESC) Council on Hypertension, the International Society of Hypertension(ISH) and the joint statement by the American College of Cardiology (ACC), American Heart Association (AHA),and Heart Failure Society of America (HFSA) all caution against discontinuing RAS-related treatments inpatients with hypertension who become infected with COVID-19.

scholarly journals Dual Blockade of the Renin-Angiotensin System: A Strategy that Should Be Reconsidered in Cardiorenal Diseases?

Nephron ◽  
2021 ◽  
pp. 1-8
Author(s):  
Mei Mei ◽  
Zulian Zhou ◽  
Qian Zhang ◽  
Yi Chen ◽  
Hongwen Zhao ◽  
...  
Keyword(s):  
Enzyme Inhibitors ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Individualized Therapy ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
System A ◽  
Receptor Blockers

Studies on pharmacological mechanisms demonstrated that a strategy of dual renin-angiotensin system (RAS) blockade may have a synergistic effect in the treatment of cardiorenal diseases and may reduce adverse reactions. However, some previous clinical studies reported that dual RAS blockade did not significantly benefit many patients with cardiorenal diseases and increased the risk of hyperkalemia, hypotension and renal function damage. Therefore, the current clinical guidelines suggest that the combined use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) should be used with caution in the clinic. However, these studies enrolled older patients with cardiovascular risk factors, and the results of these trials may not be generalized to the overall population. Some clinical evidence suggests that the combination of low-dose ACEIs and ARBs leads to more effective RAS blockade with few adverse effects. The advent of new RAS inhibitors with superior pharmacological effects provides a more suitable drug choice for individualized therapy for dual RAS blockade. Therefore, the choice of appropriate ARBs/ACEIs for individualized therapy based on patient condition may be a better way to improve the efficiency and safety of the dual RAS blockade strategy.

scholarly journals Cessation of Renin-Angiotensin System Antagonists During the SARS-CoV-2 Pandemic – Do We Have the Evidence?

2020 ◽  
Vol 5 (3) ◽  
pp. 105-109
Author(s):  
Emanuel Blîndu ◽  
Renata Gerculy ◽  
Diana Opincariu ◽  
Daniel Cernica ◽  
Imre Benedek
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blockers ◽  
Healthcare Providers ◽  
Age Groups ◽  
Renin Angiotensin System ◽  
Host Cells ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin

AbstractThe aim of this review is to provide a short update on whether treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) has beneficial or harmful effects in patients infected with SARS-CoV-2. Epidemiological studies have shown that SARS-CoV-2 infects all age groups, presenting a higher incidence in elderly patients with various comorbidities such as hypertension, diabetes mellitus, and cardiovascular diseases. A large proportion of these patients are treated with ACEIs and ARBs. Since it has been demonstrated that SARS-CoV-2 uses angiotensin converting enzyme type 2 (ACE2) as an entry point into host cells, it is important to know whether ACEIs and ARBs could modify the expression of this enzyme, and thus promote the viral infection. Animal studies and a few studies in humans have shown that renin angiotensin system (RAS) inhibitors increase tissue expression of ACE2, but with potentially beneficial effects. In this context, it is imperative to provide appropriate guidance for clinicians and patients. The major cardiology associations across the world have released statements in which they recommend healthcare providers and patients to continue their treatments for hyper-tension and heart failure as prescribed.

scholarly journals Use of inhibitors of the renin angiotensin system and COVID-19 prognosis: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Jessica Barochiner ◽  
Rocio Martinez
Keyword(s):  
Angiotensin Receptor Blockers ◽  
Meta Analysis ◽  
Random Effect ◽  
Renin Angiotensin System ◽  
Cochrane Library ◽  
Composite Outcome ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ras Inhibitors

Background: controversy has arisen in the scientific community on whether the use of renin angiotensin system (RAS) inhibitors in the context of COVID-19 would be of benefit or harmful. A meta-analysis of eligible studies comparing the occurrence of severe and fatal COVID-19 in infected patients who were under treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) vs no treatment or other antihypertensives was conducted. Methods: PubMed, Google Scholar, the Cochrane Library, MedRxiv and BioRxiv were searched for relevant studies. Fixed-effect models or random-effect models were used depending on the heterogeneity between estimates. Results: a total of fifteen studies with 21,614 patients were included. The use of RAS inhibitors was associated with a non-significant 20% decreased risk of the composite outcome (death, admission to intensive care unit, mechanical ventilation requirement or progression to severe or critical pneumonia): RR 0.81 (95%CI: 0.63-1.04), p=0.10, I2=82%. In a subgroup analysis that included hypertensive subjects only, ACEI/ARB were associated with a 27% significant decrease in the risk of the composite outcome (RR 0.73 (95%CI: 0.56-0.96), p=0.02, I2=65%). Conclusion: the results of this pooled analysis suggest that the use of ACEI/ARB does not worsen the prognosis, and could even be protective in hypertensive subjects. Patients should continue these drugs during their COVID-19 illness.

scholarly journals Discontinuation of the renin–angiotensin system inhibitors improves erythropoiesis in patients with lower-risk myelodysplastic syndromes

2021 ◽  
Vol 12 ◽  
pp. 204062072095829
Author(s):  
George Pavlidis ◽  
Sotirios G. Papageorgiou ◽  
Efthimia Bazani ◽  
Anthi Bouchla ◽  
Eirini Glezou ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Lower Risk ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Group A ◽  
Group B ◽  
Ras Inhibitors

Renin–angiotensin system (RAS) blockade by angiotensin-converting enzyme inhibitors (ACEis) or angiotensin-receptor blockers (ARBs) has been related to anemia in various situations. We aimed to investigate whether discontinuation of RAS inhibitors improves erythropoiesis in patients with lower-risk myelodysplastic syndromes (LR-MDSs). Seventy-four patients with LR-MDS were divided into three groups matched for gender and age. Group A consisted of 20 hypertensive patients who discontinued RAS inhibitors and received alternative medications. Group B consisted of 26 patients who continued to receive ACEi/ARB and Group C included 28 patients (50% hypertensive) never exposed to ACEi/ARB. Half of the patients in each group were under treatment with recombinant human erythropoietin (rHuEPO). Data were collected at baseline and after 3, 6 and 12 months. Group A showed a significant increase in hemoglobin from 10.4 ± 1g/dL at baseline to 12.6 ± 1.2 g/dL after 12 months ( p = 0.035) and in hematocrit (31.4 ± 3% versus 37.9 ± 4%, p = 0.002). Incident anemia decreased from 100% at baseline to 60% at 12 months ( p = 0.043) despite a concomitant dose reduction in rHuEPO by 18% ( p = 0.035). No changes in hemoglobin and hematocrit were observed in both Group B and Group C. In the subset of patients not treated with rHuEPO, improvement of erythropoiesis was found only in Group A, as measured by changes in hemoglobin (11.5 ± 1 g/dL versus 12.4 ± 1.3 g/dL, p = 0.041) and hematocrit (34.5 ± 3% versus 37.1 ± 4%, p = 0.038) after 12 months. In contrast, Group B and Group C decreased hemoglobin and hematocrit after 12 months ( p < 0.05). In conclusion, discontinuation of ACEi/ARB in LR-MDS patients is followed by a significant recovery of erythropoiesis after 12 months.

scholarly journals Renin-Angiotensin System Blockade after Acute Kidney Injury (AKI) and Risk of Recurrent AKI

2019 ◽  
Vol 15 (1) ◽  
pp. 26-34 ◽  
Author(s):  
Chi-yuan Hsu ◽  
Kathleen D. Liu ◽  
Jingrong Yang ◽  
David V. Glidden ◽  
Thida C. Tan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Care Delivery ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Time Dependent ◽  
Converting Enzyme Inhibitors ◽  
Inference Models ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Increased Risk

Background and objectivesHow to best medically manage patients who survived hospitalized AKI is unclear. Use of renin-angiotensin system blockers in this setting may increase risk of recurrent AKI.Design, setting, participants, & measurementsThis is a cohort study of 10,242 members of an integrated health care delivery system in Northern California who experienced AKI and survived a hospitalization between January 1, 2006 and December 31, 2013. All study participants did not have prior heart failure or use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) up to 5 years prior. New receipt and time-updated exposure of ACE-Is/ARBs was identified on the basis of dispensed prescriptions found in outpatient health plan pharmacy databases. The main outcome of interest was subsequent episode of hospitalized AKI after discharge from an initial index hospitalization complicated by AKI. Recurrent AKI episode was defined using acute changes in serum creatinine concentrations. Marginal structural models were used to adjust for baseline and potential time-dependent confounders.ResultsForty-seven percent of the study population had a documented eGFR<60 ml/min per 1.73 m2 or documented proteinuria before hospitalization. With a median of 3 (interquartile range, 1–5) years of follow-up, 1853 (18%) patients initiated use of ACE-Is/ARBs and 2124 (21%) patients experienced recurrent AKI. Crude rate of recurrent AKI was 6.1 (95% confidence interval [95% CI], 5.9 to 6.4) per 100 person-years off ACE-Is/ARBs and 5.7 (95% CI, 4.9 to 6.5) per 100 person-years on ACE-Is/ARBs. In marginal structural causal inference models that adjusted for baseline and potential time-dependent confounders, exposure to ACE-I/ARB use was not associated with higher incidence of recurrent AKI (adjusted odds ratio, 0.71; 95% CI, 0.45 to 1.12).ConclusionsIn this study of AKI survivors without heart failure, new use of ACE-I/ARB therapy was not independently associated with increased risk of recurrent hospitalized AKI.

Renin-Angiotensin System and Alzheimer’s Disease Pathophysiology: From the Potential Interactions to Therapeutic Perspectives

2020 ◽  
Vol 27 (6) ◽  
pp. 484-511 ◽  
Author(s):  
Victor Teatini Ribeiro ◽  
Leonardo Cruz de Souza ◽  
Ana Cristina Simões e Silva
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enzyme Inhibitors ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Beneficial Effects

New roles of the Renin-Angiotensin System (RAS), apart from fluid homeostasis and Blood Pressure (BP) regulation, are being progressively unveiled, since the discoveries of RAS alternative axes and local RAS in different tissues, including the brain. Brain RAS is reported to interact with pathophysiological mechanisms of many neurological and psychiatric diseases, including Alzheimer’s Disease (AD). Even though AD is the most common cause of dementia worldwide, its pathophysiology is far from elucidated. Currently, no treatment can halt the disease course. Successive failures of amyloid-targeting drugs have challenged the amyloid hypothesis and increased the interest in the inflammatory and vascular aspects of AD. RAS compounds, both centrally and peripherally, potentially interact with neuroinflammation and cerebrovascular regulation. This narrative review discusses the AD pathophysiology and its possible interaction with RAS, looking forward to potential therapeutic approaches. RAS molecules affect BP, cerebral blood flow, neuroinflammation, and oxidative stress. Angiotensin (Ang) II, via angiotensin type 1 receptors may promote brain tissue damage, while Ang-(1-7) seems to elicit neuroprotection. Several studies dosed RAS molecules in AD patients&#039; biological material, with heterogeneous results. The link between AD and clinical conditions related to classical RAS axis overactivation (hypertension, heart failure, and chronic kidney disease) supports the hypothesized role of this system in AD. Additionally, RAStargeting drugs as Angiotensin Converting Enzyme inhibitors (ACEis) and Angiotensin Receptor Blockers (ARBs) seem to exert beneficial effects on AD. Results of randomized controlled trials testing ACEi or ARBs in AD are awaited to elucidate whether AD-RAS interaction has implications on AD therapeutics.

scholarly journals Association of renin–angiotensin system blockers with COVID-19 diagnosis and prognosis in patients with hypertension: a population-based study

2021 ◽  
Author(s):  
Maria José Soler ◽  
Aida Ribera ◽  
Josep R Marsal ◽  
Ana Belen Mendez ◽  
Mireia Andres ◽  
...  
Keyword(s):  
Angiotensin Receptor Blockers ◽  
Large Population ◽  
Renin Angiotensin System ◽  
Population Based ◽  
Respiratory Support ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Raas Blockade ◽  
Diagnosis And Prognosis

Abstract Background The effect of renin-angiotensin(RAS) blockade either by angiotensin-converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARBs) on coronavirus disease 2019(COVID-19) susceptibility, mortality and severity is inadequately described. We examined the association between renin-angiotensin system (RAS) blockade and COVID-19 diagnosis and prognosis in a large population-based cohort of patients with hypertension. Methods This is a cohort study using regional health records. We identified all individuals aged 18-95 years from 87 health care reference areas of the main health provider in Catalonia(Spain), with a history of hypertension from primary care records. Data were linked to COVID-19 test results, hospital, pharmacy and mortality records from 1 March 2020 to 14 August 2020. We defined exposure to RAS blockers as the dispensation of ACEi/ARBs during the three months before COVID-19 diagnosis or 1 March 2020. Primary outcomes were: COVID-19 infection, and severe progression in hospitalized patients with COVID-19(the composite of need for invasive respiratory support or death). For both outcomes and for each exposure of interest (RAAS blockade, ACEi or ARB) we estimated associations in age-sex-area-propensity matched samples. Results From a cohort of 1,365,215 inhabitants we identified 305,972 patients with hypertension history. Recent use of ACEi/ARBs in patients with hypertension was associated with a lower 6 month-cumulative incidence of COVID-19 diagnosis (3.78% [95% CI: 3.69% - 3.86%] vs 4.53% [95% CI: 4.40% - 4.65%]; p &lt; 0.001). In the 12,344 patients with COVID-19 infection, the use of ACEi/ARBs was not associated with a higher risk of hospitalization with need for invasive respiratory support or death (OR = 0.91 (0.71 – 1.15); p = 0.426). Conclusion RAS blockade in patients with hypertension is not associated with higher risk of COVID-19 infection or with a worse progression of the disease.

Sign in / Sign up

Export Citation Format

Share Document