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Hypertension Research : Official... Jul 2022Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the possible roles of renin-angiotensin system (RAS) inhibitors in COVID-19 have been debated as... (Review)
Review
Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the possible roles of renin-angiotensin system (RAS) inhibitors in COVID-19 have been debated as favorable, harmful, or neutral. Angiotensin-converting enzyme 2 (ACE2) not only is the entry route of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but also triggers a major mechanism of COVID-19 aggravation by promoting tissue RAS dysregulation, which induces a hyperinflammatory state in several organs, leading to lung injury, hematological alterations, and immunological dysregulation. ACE inhibitors and angiotensin II type-1 receptor blockers (ARBs) inhibit the detrimental hyperactivation of the RAS by SARS-CoV-2 and increase the expression of ACE2, which is a counter-regulator of the RAS. Several studies have investigated the beneficial profile of RAS inhibitors in COVID-19; however, this finding remains unclear. Further prospective studies are warranted to confirm the role of RAS inhibitors in COVID-19. In this review, we summarize the potential effects of RAS inhibitors that have come to light thus far and review the impact of RAS inhibitors on COVID-19.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; COVID-19; Humans; Peptidyl-Dipeptidase A; Renin-Angiotensin System; SARS-CoV-2
PubMed: 35581498
DOI: 10.1038/s41440-022-00922-3 -
Biochemia Medica Feb 2023In the initial diagnostics of arterial hypertension (AH) laboratory medicine is a cornerstone, along with a blood pressure (BP) measurement and an electrocardiogram. It... (Review)
Review
In the initial diagnostics of arterial hypertension (AH) laboratory medicine is a cornerstone, along with a blood pressure (BP) measurement and an electrocardiogram. It mainly refers to routine blood and urine tests for diagnosis and monitoring primary hypertension and its associated conditions such as asymptomatic hypertension-mediated organ damage, chronic kidney disease and hypertensive disorders of pregnancy. In addition, long term non-fatal and fatal risks for cardiovascular (CV) events in hypertension are assessed based on clinical and laboratory data. Furthermore, laboratory medicine is involved in the management of hypertension, especially in monitoring the disease progression. However, antihypertensive drugs may interfere with laboratory test results. Diuretics, especially thiazides, can affect blood and urine sodium concentrations, or angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can affect the blood biomarkers of the renin-angiotensin-aldosterone system (RAAS). It's dysfunction plays a critical role in primary aldosteronism (PA), the most common endocrine disorder in secondary hypertension, which accounts for only small proportion of AH in relative terms but substantial proportion of hypertensives in absolute terms, affecting younger population and carrying a higher risk of CV mortality and morbidity. When screening for PA, aldosterone-to-renin ratio still contributes massively to the increased incidence of the disease, despite certain limits. In conclusion, laboratory medicine is involved in the screening, diagnosis, monitoring and prognosis of hypertension. It is of great importance to understand the preanalytical and analytical factors influencing final laboratory result.
Topics: Humans; Hypertension; Antihypertensive Agents; Angiotensin-Converting Enzyme Inhibitors; Renin-Angiotensin System; Prognosis
PubMed: 36817852
DOI: 10.11613/BM.2023.010501 -
Journal of the... 2022Angiotensin-converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase and is crucial in the renin-angiotensin-aldosterone system (RAAS) but also implicated... (Review)
Review
Angiotensin-converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase and is crucial in the renin-angiotensin-aldosterone system (RAAS) but also implicated in immune regulation. Intrinsic ACE has been detected in several immune cell populations, including macrophages and neutrophils, where its overexpression results in enhanced bactericidal and antitumour responses, independent of angiotensin II. With roles in antigen presentation and inflammation, the impact of ACE inhibitors must be explored to understand how ACE inhibition may impact our ability to clear infections or malignancy, particularly in the wake of the coronavirus (SARS-CoV2) pandemic and as antibiotic resistance grows. Patients using ACE inhibitors may be more at risk of postsurgical complications as ACE inhibition in human neutrophils results in decreased ROS and phagocytosis whilst angiotensin receptor blockers (ARBs) have no effect. In contrast, ACE is also elevated in certain autoimmune diseases such as rheumatoid arthritis and lupus, and its inhibition benefits patient outcome where inflammatory immune cells are overactive. Although the ACE autoimmune landscape is changing, some studies have conflicting results and require further input. This review seeks to highlight the need for further research covering ACE inhibitor therapeutics and their potential role in improving autoimmune conditions, cancer, or how they may contribute to immunocompromise during infection and neurodegenerative diseases. Understanding ACE inhibition in immune cells is a developing field that will alter how ACE inhibitors are designed in future and aid in developing therapeutic interventions.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; COVID-19; Humans; RNA, Viral; Renin-Angiotensin System; SARS-CoV-2
PubMed: 36016727
DOI: 10.1155/2022/9028969 -
ANZ Journal of Surgery Nov 2022
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Angioedema
PubMed: 35199446
DOI: 10.1111/ans.17575 -
Journal of Cardiac Surgery Jun 2020
Topics: Angiotensin-Converting Enzyme Inhibitors; Betacoronavirus; COVID-19; Coronary Disease; Coronavirus Infections; Humans; Hypertension; Pandemics; Pneumonia, Viral; Receptor, Angiotensin, Type 2; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 32340070
DOI: 10.1111/jocs.14582 -
British Journal of Pharmacology Jun 2020The renin-angiotensin system (RAS) now underlies the successful treatment of almost 50% of the patients in cardiovascular medicine, with serious possibilities of... (Review)
Review
The renin-angiotensin system (RAS) now underlies the successful treatment of almost 50% of the patients in cardiovascular medicine, with serious possibilities of extension to diabetes, Alzheimer's disease and cancer. This clinical transformation started just over 50 years ago, with the unexpected identification of a bradykinin-potentiating peptide from snake venom, as a potent inhibitor of ACE which led to the development of the first synthetic inhibitor, captopril, followed by the angiotensin receptor blockers. This article analyses the transformation of the RAS into its different stages, from academic experiments to clinical use and back to the laboratory, identifying the critical events involved, both clinical and scientific. The analysis also assesses the contributions of chance, coincidence, and conviction that were crucial in this transformation. Although questions remain, the transformation of the RAS over the past five decades provides a success story for medicine, for pharmacology, and, most significantly, for patients.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Captopril; Diabetes Mellitus; Humans; Hypertension; Renin-Angiotensin System
PubMed: 32144755
DOI: 10.1111/bph.15045 -
Clinical Science (London, England :... Nov 2020Angiotensin converting enzyme (ACE) is well-known for its role in blood pressure regulation via the renin-angiotensin aldosterone system (RAAS) but also functions in... (Review)
Review
Angiotensin converting enzyme (ACE) is well-known for its role in blood pressure regulation via the renin-angiotensin aldosterone system (RAAS) but also functions in fertility, immunity, haematopoiesis and diseases such as obesity, fibrosis and Alzheimer's dementia. Like ACE, the human homologue ACE2 is also involved in blood pressure regulation and cleaves a range of substrates involved in different physiological processes. Importantly, it is the functional receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 responsible for the 2020, coronavirus infectious disease 2019 (COVID-19) pandemic. Understanding the interaction between SARS-CoV-2 and ACE2 is crucial for the design of therapies to combat this disease. This review provides a comparative analysis of methodologies and findings to describe how structural biology techniques like X-ray crystallography and cryo-electron microscopy have enabled remarkable discoveries into the structure-function relationship of ACE and ACE2. This, in turn, has enabled the development of ACE inhibitors for the treatment of cardiovascular disease and candidate therapies for the treatment of COVID-19. However, despite these advances the function of ACE homologues in non-human organisms is not yet fully understood. ACE homologues have been discovered in the tissues, body fluids and venom of species from diverse lineages and are known to have important functions in fertility, envenoming and insect-host defence mechanisms. We, therefore, further highlight the need for structural insight into insect and venom ACE homologues for the potential development of novel anti-venoms and insecticides.
Topics: Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Animals; Antiviral Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Host-Pathogen Interactions; Humans; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Protein Conformation; Receptors, Virus; SARS-CoV-2; Structure-Activity Relationship; Virus Internalization; COVID-19 Drug Treatment
PubMed: 33146371
DOI: 10.1042/CS20200899 -
BMJ Case Reports Sep 2020SARS-CoV-2, the virus responsible for COVID-19, binds to the ACE2 receptors. ACE2 is thought to counterbalance ACE in the renin-angiotensin system. While presently it is...
SARS-CoV-2, the virus responsible for COVID-19, binds to the ACE2 receptors. ACE2 is thought to counterbalance ACE in the renin-angiotensin system. While presently it is advised that patients should continue to use ACE inhibitors or angiotensin receptor blockers, questions still remain as to whether adverse effects are potentiated by the virus. Here, we report a case of a 57-year-old man, unknowingly with COVID-19, who presented to the emergency department with tongue swelling, shortness of breath and difficulty in speaking following 4 months taking benazepril, an ACE inhibitor. Finally, we also describe possible pathways that exist for SARS-CoV-2 to interact with the mechanism behind angioedema.
Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Anti-Allergic Agents; Benzazepines; Betacoronavirus; COVID-19; Coronavirus Infections; Diagnosis, Differential; Diphenhydramine; Famotidine; Histamine H2 Antagonists; Humans; Male; Middle Aged; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tranexamic Acid
PubMed: 32912894
DOI: 10.1136/bcr-2020-237888 -
Current Cardiology Reports Jul 2020Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are commonly used anti-hypertensive medications in a number of clinical settings. They are... (Review)
Review
PURPOSE OF REVIEW
Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are commonly used anti-hypertensive medications in a number of clinical settings. They are often used interchangeably, but we pose the provocative question as to whether they should be. We review the literature to evaluate for any differences in efficacy between the two classes in order to determine if the greater side effects associated with angiotensin-converting enzyme inhibitors are offset by any advantageous effects on outcomes to warrant their use over angiotensin receptor blockers.
RECENT FINDINGS
In many clinical scenarios, the data supports similar efficacy between ACE inhibitors and ARBs, while in a minority of others, there are murky signals from previous trials that suggest ACE inhibitors may be better. However, when reviewing the literature in its entirety, and taking into account recently published pooled analysis and head to head trials, it is reasonable to conclude that ACE inhibitors and ARBs have similar efficacy. This is in contrast to data on adverse effects, which consistently favors the use of ARBs. From the available data, it is reasonable to conclude that ACE inhibitors and ARBs have equal efficacy yet unequal adverse effects. It is in this context that we take the provocative stance that ACE inhibitors should not be used to treat hypertension.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Humans; Hypertension; Renin-Angiotensin System
PubMed: 32648000
DOI: 10.1007/s11886-020-01352-8 -
CMAJ : Canadian Medical Association... May 2021
Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Humans; Risk Factors
PubMed: 34001550
DOI: 10.1503/cmaj.202308