scholarly journals Renin-angiotensin-aldosterone system inhibitors – a realm of confusion in COVID-19

2021 ◽  
Vol 4 (Special2) ◽  
pp. 389-394
Author(s):  
Angela Madalina Lazar
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Current Knowledge ◽  
Angiotensin Receptor Blockers ◽  
Protective Effects ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Raas Inhibitors

Currently, there is a persisting dispute regarding the renin-angiotensin-aldosterone-system (RAAS) inhibitors' safety of use in COVID-19 pandemics. On one side, RAAS inhibitors appear to determine an overexpression of ACE2, the receptor of SARS-CoV-2. Therefore, they could increase the risk of SARS-CoV-2 infection and its degree of severity. On the other side, the discontinuation of RAAS leads to cardiovascular decompensation and has been discouraged by the major medical societies. Also, large-cohort studies report beneficial or at least neutral effects for the RAAS inhibitors in COVID-19 patients. Worldwide, millions of patients receive RAAS inhibitors for the treatment of hypertension and other important comorbidities. In this context, knowledge of the exact effect of these medications becomes of crucial significance. This paper aims to fill in a gap in the current knowledge and presents a putative mechanism by which RAAS inhibitor administration's beneficial results can be explained better. RAAS inhibitors can be beneficial, as they counteract the excessive detrimental activation of the classical angiotensin-converting enzyme (ACE) axis, decreasing the angiotensin II levels. The angiotensin receptor blockers (ARBs) increase the angiotensin II levels, while the angiotensin-converting enzyme inhibitors (ACEI) increase the angiotensin I levels; these substrates will compete with the SARS-CoV-2 for the ACE2 binding, decreasing the viral infectivity. In addition, following the RAAS inhibitors treatment, the up-regulated ACE2 will cleave these substrates (angiotensin I and II), particularly to angiotensin 1-7 that possesses vasodilator, protective effects.

scholarly journals Clinical outcome of renin-angiotensin-aldosterone system blockers in treatment of hypertensive patients with COVID-19: a systematic review and meta-analysis

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Andrea Laurentius ◽  
Brian Mendel ◽  
Radityo Prakoso
Keyword(s):  
Clinical Outcome ◽  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blockers ◽  
Hospital Treatment ◽  
Main Body ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Renin Angiotensin Aldosterone System ◽  
Hypertensive Patients ◽  
Renin Angiotensin

Abstract Background Novel coronavirus disease 2019 has been stated as global disease pandemic due to its rapid spread worldwide. Up to 30% of coronavirus disease 2019 patients with hypertension are more susceptible to death. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been used as primary line of medication for hypertension; nonetheless, conflicting data arises as numerous studies showed contradictory results. Main body Aiming to show clinical outcome of renin-angiotensin-aldosterone system blockers in hospital treatment of hypertensive patients with coronavirus disease 2019, systematically searched literatures through five databases were intensively appraised using The Grading of Recommendations Assessment, Development and Evaluation checklists for cohort studies. Based on the result evaluation from retrospective cohorts involving more than 15,000 patients across Asia and other regions of the world, ten encompassed studies divided into two subgroups in this meta-review showed that in-hospital hypertensive coronavirus disease 2019 patients receiving antihypertensive drugs were associated with overall risk reduction in subgroup 1 (hazard ratio, HR = 0.96, 95% CI = 0.82–1.12) to no outcome association of all-cause mortalities in subgroup 2 (HR = 0.26, 95% CI = 0.19–0.34). All appraised studies in synergism showed that mortality outcomes were not augmented with the employment of either ACE inhibitor or ARB in subjects. Conclusion Therefore, the results support recommendation by the American Heart Association not to discontinue angiotensin-converting enzyme inhibitor or angiotensin receptor blocker regimens in coronavirus disease 2019 patients with hypertension.

scholarly journals Advances in the Renin-Angiotensin-Aldosterone System: Relevance to Diabetic Nephropathy

2008 ◽  
Vol 8 ◽  
pp. 434-445 ◽  
Author(s):  
Audrey Koitka ◽  
Christos Tikellis
Keyword(s):  
Diabetic Nephropathy ◽  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Renal Disease ◽  
Converting Enzyme ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Angiotensin Type 2 Receptor

Hypertension is now recognized as a key contributory factor to the development and progression of kidney disease in both type 1 and type 2 diabetes. The renin angiotensin system (RAS) and its effector molecule angiotensin II, in particular, have a range of hemodynamic and nonhemodynamic effects that contribute not only to the development of hypertension, but also to renal disease. As a result, therapeutic inhibition of the RAS with angiotensin-converting enzyme inhibitors and/or selective angiotensin II type 1 receptor blockers has been proposed as a key strategy for reducing kidney damage beyond the expected effects one would observe with blood pressure reduction per se. Although the relationship between the RAS and the progression of diabetic renal disease has been known for many decades, recent advances have revealed a more complex paradigm with the discovery of a number of new components. Thus, further understanding of these new components of the renin angiotensin aldosterone system (RAAS), such as the angiotensin type 2 receptor subtype, angiotensin converting enzyme 2, and the recently cloned renin receptor, is likely to have therapeutic implications for disorders such as diabetic nephropathy, where interruption of the RAAS is widely used.

scholarly journals The Role of Renin-Angiotensin-Aldosterone System in the Heart and Lung: Focus on COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Annamaria Mascolo ◽  
Cristina Scavone ◽  
Concetta Rafaniello ◽  
Antonella De Angelis ◽  
Konrad Urbanek ◽  
...  
Keyword(s):  
Lung Injury ◽  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blockers ◽  
Protective Action ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin

The renin-angiotensin-aldosterone system (RAAS) firstly considered as a cardiovascular circulating hormonal system, it is now accepted as a local tissue system that works synergistically or independently with the circulating one. Evidence states that tissue RAAS locally generates mediators with regulatory homeostatic functions, thus contributing, at some extent, to organ dysfunction or disease. Specifically, RAAS can be divided into the traditional RAAS pathway (or classic RAAS) mediated by angiotensin II (AII), and the non-classic RAAS pathway mediated by angiotensin 1–7. Both pathways operate in the heart and lung. In the heart, the classic RAAS plays a role in both hemodynamics and tissue remodeling associated with cardiomyocyte and endothelial dysfunction, leading to progressive functional impairment. Moreover, the local classic RAAS may predispose the onset of atrial fibrillation through different biological mechanisms involving inflammation, accumulation of epicardial adipose tissue, and electrical cardiac remodeling. In the lung, the classic RAAS regulates cell proliferation, immune-inflammatory response, hypoxia, and angiogenesis, contributing to lung injury and different pulmonary diseases (including COVID-19). Instead, the local non-classic RAAS counteracts the classic RAAS effects exerting a protective action on both heart and lung. Moreover, the non-classic RAAS, through the angiotensin-converting enzyme 2 (ACE2), mediates the entry of the etiological agent of COVID-19 (SARS-CoV-2) into cells. This may cause a reduction in ACE2 and an imbalance between angiotensins in favor of AII that may be responsible for the lung and heart damage. Drugs blocking the classic RAAS (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) are well known to exert a cardiovascular benefit. They are recently under evaluation for COVID-19 for their ability to block AII-induced lung injury altogether with drugs stimulating the non-classic RAAS. Herein, we discuss the available evidence on the role of RAAS in the heart and lung, summarizing all clinical data related to the use of drugs acting either by blocking the classic RAAS or stimulating the non-classic RAAS.

scholarly journals Controversial Roles of the Renin Angiotensin System and Its Modulators During the COVID-19 Pandemic

2021 ◽  
Vol 12 ◽  
Author(s):  
Simon B. Gressens ◽  
Georges Leftheriotis ◽  
Jean-Claude Dussaule ◽  
Martin Flamant ◽  
Bernard I. Levy ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Enzyme Inhibitors ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Renin Angiotensin ◽  
The Impact

Since December 2019, the coronavirus 2019 (COVID-19) pandemic has rapidly spread and overwhelmed healthcare systems worldwide, urging physicians to understand how to manage this novel infection. Early in the pandemic, more severe forms of COVID-19 have been observed in patients with cardiovascular comorbidities, who are often treated with renin-angiotensin aldosterone system (RAAS)-blockers, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), but whether these are indeed independent risk factors is unknown. The cellular receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the membrane-bound angiotensin converting enzyme 2 (ACE2), as for SARS-CoV(-1). Experimental data suggest that expression of ACE2 may be increased by RAAS-blockers, raising concerns that these drugs may facilitate viral cell entry. On the other hand, ACE2 is a key counter-regulator of the RAAS, by degrading angiotensin II into angiotensin (1-7), and may thereby mediate beneficial effects in COVID-19. These considerations have raised concerns about the management of these drugs, and early comments shed vivid controversy among physicians. This review will describe the homeostatic balance between ACE-angiotensin II and ACE2-angiotensin (1-7) and summarize the pathophysiological rationale underlying the debated role of the RAAS and its modulators in the context of the pandemic. In addition, we will review available evidence investigating the impact of RAAS blockers on the course and prognosis of COVID-19 and discuss why retrospective observational studies should be interpreted with caution. These considerations highlight the importance of solid evidence-based data in order to guide physicians in the management of RAAS-interfering drugs in the general population as well as in patients with more or less severe forms of SARS-CoV-2 infection.

scholarly journals The Vasoactive Mas Receptor in Essential Hypertension

2020 ◽  
Vol 9 (1) ◽  
pp. 267 ◽  
Author(s):  
Amalie Povlsen ◽  
Daniela Grimm ◽  
Markus Wehland ◽  
Manfred Infanger ◽  
Marcus Krüger
Keyword(s):  
Essential Hypertension ◽  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Current Knowledge ◽  
Converting Enzyme ◽  
Angiotensin Ii Receptor ◽  
Vascular Control ◽  
Renin Angiotensin ◽  
Mas Receptor ◽  
Clinical Potential

The renin–angiotensin–aldosterone system (RAAS) has been studied extensively, and with the inclusion of novel components, it has become evident that the system is much more complex than originally anticipated. According to current knowledge, there are two main axes of the RAAS, which counteract each other in terms of vascular control: The classical vasoconstrictive axis, renin/angiotensin-converting enzyme/angiotensin II/angiotensin II receptor type 1 (AT1R), and the opposing vasorelaxant axis, angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas receptor (MasR). An abnormal activity within the system constitutes a hallmark in hypertension, which is a global health problem that predisposes cardiovascular and renal morbidities. In particular, essential hypertension predominates in the hypertensive population of more than 1.3 billion humans worldwide, and yet, the pathophysiology behind this multifactorial condition needs clarification. While commonly applied pharmacological strategies target the classical axis of the RAAS, discovery of the vasoprotective effects of the opposing, vasorelaxant axis has presented encouraging experimental evidence for a new potential direction in RAAS-targeted therapy based on the G protein-coupled MasR. In addition, the endogenous MasR agonist angiotensin-(1-7), peptide analogues, and related molecules have become the subject of recent studies within this field. Nevertheless, the clinical potential of MasR remains unclear due to indications of physiological-biased activities of the RAAS and interacting signaling pathways.

scholarly journals Renin Angiotensin Aldosterone System Antagonism in 2019 Novel Coronavirus Acute Lung Injury

2021 ◽  
Author(s):  
Davide Ventura ◽  
Amy L Carr ◽  
R Duane Davis ◽  
Scott Silvestry ◽  
Linda Bogar ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Ii Receptor ◽  
Pulmonary Tissue ◽  
Renin Angiotensin Aldosterone System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Receptor Blockers ◽  
Membrane Bound ◽  
Raas Inhibitors ◽  
Novel Coronavirus

Abstract It has been established SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2), a membrane-bound regulatory peptide, for host cell entry. Renin-angiotensin-aldosterone system (RAAS) inhibitors have been reported to increase ACE2 in type 2 pneumocytes pulmonary tissue. Controversy exists for the continuation of ACE inhibitors, angiotensin II receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs) in the current pandemic. ACE2 serves as regulatory enzyme in maintaining homeostasis between proinflammatory Angiotensin II and anti-inflammatory Angiotensin 1,7 peptides. Derangements in these peptides are associated with cardiovascular disease and are implicated in the progression of acute respiratory distress syndrome (ARDS). Augmentation of the ACE2/Ang1,7 axis represent a critical target in the supportive management of COVID-19 associated lung disease. Observational data describing the use of RAAS inhibitors in the setting of SARS-CoV-2 have not borne signals of harm to date. However, equipoise persists requiring an analysis of novel agents including recombinant human-ACE2 and existing RAAS inhibitors while balancing ongoing controversies associated with increased coronavirus infectivity and virulence.

scholarly journals Pathological Role of Angiotensin II in Severe COVID-19

TH Open ◽  
2020 ◽  
Vol 04 (02) ◽  
pp. e138-e144 ◽  
Author(s):  
Wolfgang Miesbach
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Treatment Options ◽  
Renin Angiotensin System ◽  
Target Cells ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Novel Coronavirus

AbstractThe activated renin–angiotensin system induces a prothrombotic state resulting from the imbalance between coagulation and fibrinolysis. Angiotensin II is the central effector molecule of the activated renin–angiotensin system and is degraded by the angiotensin-converting enzyme 2 to angiotensin (1–7). The novel coronavirus infection (classified as COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as acute respiratory distress syndrome, sepsis, and death in a proportion of patients, mostly elderly patients with preexisting comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to enter the target cells, resulting in activation of the renin–angiotensin system. After downregulating the angiotensin-converting enzyme 2, the vasoconstrictor angiotensin II is increasingly produced and its counterregulating molecules angiotensin (1–7) reduced. Angiotensin II increases thrombin formation and impairs fibrinolysis. Elevated levels were strongly associated with viral load and lung injury in patients with severe COVID-19. Therefore, the complex clinical picture of patients with severe complications of COVID-19 is triggered by the various effects of highly expressed angiotensin II on vasculopathy, coagulopathy, and inflammation. Future treatment options should focus on blocking the thrombogenic and inflammatory properties of angiotensin II in COVID-19 patients.

Resveratrol ameliorates the cyclosporine-induced vascular and renal impairments: possible impact of the modulation of renin–angiotensin system

2019 ◽  
Vol 97 (12) ◽  
pp. 1115-1123 ◽  
Author(s):  
Seldag Bekpinar ◽  
Ece Karaca ◽  
Selin Yamakoğlu ◽  
F. İlkay Alp-Yıldırım ◽  
Vakur Olgac ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Immunosuppressive Drug ◽  
Oxidative Stress Marker ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
System Components ◽  
Renal Tubular

Cyclosporine, an immunosuppressive drug, exhibits a toxic effect on renal and vascular systems. The present study investigated whether resveratrol treatment alleviates renal and vascular injury induced by cyclosporine. Cyclosporine (25 mg/kg per day, s.c.) was given for 7 days to rats either alone or in combination with resveratrol (10 mg/kg per day, i.p.). Relaxation and contraction responses of aorta were examined. Serum levels of blood urea nitrogen, creatinine, angiotensin II, and angiotensin 1-7 were measured. Histopathological examinations as well as immunostaining for 4-hydroxynonenal and nitrotyrosine were performed in the kidney. RNA expressions of renin–angiotensin system components were also measured in renal and aortic tissues. Cyclosporine decreased the endothelium-dependent relaxation and increased vascular contraction in the aorta. It caused renal tubular degeneration and increased immunostaining for 4-hydroxynonenal, an oxidative stress marker. Cyclosporine also caused upregulations of the vasoconstrictive renin–angiotensin system components in renal (angiotensin-converting enzyme) and aortic (angiotensin II type 1 receptor) tissues. Resveratrol co-treatment prevented the cyclosporine-related deteriorations. Moreover, it induced the expressions of vasodilatory effective angiotensin-converting enzyme 2 and angiotensin II type 2 receptor in aorta and kidney, respectively. We conclude that resveratrol may be effective in preventing cyclosporine-induced renal tubular degeneration and vascular dysfunction at least in part by modulating the renin–angiotensin system.

scholarly journals PERAN KOMPLEKS JUKSTAGLOMERULUS TERHADAP RESISTENSI PEMBULUH DARAH

2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Renny M. Toreh ◽  
Sonny J.R. Kalangi ◽  
Sunny Wangko
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Sodium Intake ◽  
Angiotensin Receptor Blockers ◽  
Antihypertensive Agents ◽  
Angiotensin I ◽  
Renin Angiotensin ◽  
Renin Synthesis ◽  
Receptor Blockers

Abstract: As the main structural component of the renin-angiotensin-aldosterone system (RAAS), the juxtaglomerular complex plays a very important role in the regulation of vascular resistance. The synthesis and release of renin into the circulation occurs due to the decrease of blood pressure, loss of body fluid, and a decrease of sodium intake. Renin converts angiotensinogen into angiotensin I, which is further converted by the angiotensin converting enzyme (ACE) into angiotensin II. This angiotensin II causes vasoconstriction of blood vessels, resulting in an increase of vascular resistance and blood pressure. The ACE inhibitors and the angiotensin receptor blockers (ARBs) do not inhibit the RAAS completely since they cause an increase of renin activity. The renin blockers are more effective in inhibiting RAAS activity; therefore, these renin blockers can be applied as antihypertensive agents with fewer side effects. The RAAS activity can be inhibited by a decrease of renin synthesis in the juxtaglomerular complex by blocking the signals in the juxtaglomerular complex that stimulate renin synthesis, and by blocking the gap junctions in the juxtaglomerular complex. Keywords: juxtaglomerular complex, vascular resistance, RAAS.   Abstrak: Kompleks jukstaglomerulus sebagai komponen struktural utama sistem renin angiotensin berperan penting dalam pengaturan resistensi pembuluh darah. Sintesis dan pelepasan renin ke sirkulasi terjadi karena tekanan darah yang rendah, kehilangan cairan tubuh, dan kurangnya intake natrium. Renin akan memecah angiotensinogen menjadi angiotesin I yang kemudian secara cepat dikonversi oleh enzim pengonversi angiotensin  menjadi angiotensin II. Angiotensin II menyebabkan vasokontriksi pembuluh darah sehingga meningkatkan resistensi pembuluh darah yang pada akhirnya akan meningkatkan tekanan darah. ACEinhibitor dan ARB kurang sempurna dalam menghambat kerja SRAA oleh karena keduanya memutuskan rantai mekanisme timbal balik sehingga meningkatkan aktifitas renin. Penghambat renin lebih efektif digunakan untuk menghambat aktifitas SRAA sehingga penghambat renin dapat digunakan sebagai obat anti-hipertensi dan memiliki efek samping yang rendah. Metode penghambatan SRAA yang juga dapat dikembangkan ialah penghambatan sintesis renin dalam kompleks jukstaglomerulus dengan cara menekan sinyal-sinyal dalam kompleks jukstaglomerulus yang merangsang sintesis renin dan menghambat fungsi taut kedap yang terdapat dalam kompleks jukstaglomerulus. Kata kunci: kompleks juksta glomerulus, resistensi vaskular, SRAA.

scholarly journals Association of seven renin angiotensin system gene polymorphisms with restenosis in patients following coronary stenting

2017 ◽  
Vol 18 (1) ◽  
pp. 147032031668877 ◽  
Author(s):  
Min Zhu ◽  
Minjun Yang ◽  
Jiangbo Lin ◽  
Huanhuan Zhu ◽  
Yifei Lu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Neointimal Hyperplasia ◽  
Renin Angiotensin System ◽  
Coronary Stenting ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Stent Restenosis ◽  
In Stent Restenosis

Background and objective: Percutaneous coronary intervention, despite being effective for coronary revascularization, causes in-stent restenosis due to neointimal hyperplasia in a large number of patients. The renin-angiotensin system is involved in neointimal hyperplasia. This study sought to evaluate seven gene polymorphisms of key renin-angiotensin system components, including angiotensinogen, angiotensin-converting enzyme and angiotensin II type 1a receptors, and their associations with in-stent restenosis in patients with coronary artery disease following coronary stenting. Methods and results: Three hundred and fifty-two patients undergoing coronary drug-eluting stent implantation were recruited. Seventy-five patients (21.3%) were diagnosed as restenosis by angiography. Genotyping for angiotensin-converting enzyme insertion/deletion demonstrated a significant association of angiotensin-converting enzyme DD genotype with the occurrence of restenosis. Direct DNA sequencing revealed no association of angiotensinogen (M235T, G217A, G152A, G-6A, and A-20C) or angiotensin II type I receptor A1166C polymorphisms with in-stent restenosis. However, angiotensin II type 1a A1166C polymorphism was significantly associated with increased susceptibility to restenosis in a subgroup of patients aged more than 60 years. Conclusion: Thus, our study suggests that genetic polymorphisms of angiotensin-converting enzyme insertion/deletion are associated with in-stent restenosis in coronary artery disease patients following coronary stenting.

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