Effect of angiotensin receptor blockers and angiotensin converting enzyme 2 on plasma equilibrium angiotensin peptide concentrations in dogs with heart disease

The renin–angiotensin–aldosterone system (RAAS) has been recognized as a key player in the complex scenario of cardiovascular regulation. Aside from its role in the cardiovascular diseases, RAAS dysregulation has emerged as a central pathomechanism in the severe acute respiratory syndrome coronavirus 1 (SARS-CoV1) epidemic, dating back to 2002–2004, and the current COVID-19 pandemic with SARS-CoV2, with the latter involving the interaction with angiotensin-converting enzyme 2 (ACE2). ACE2 is the enzyme responsible for Ang 1-7 production that partly counteracts the RAAS effects and promotes nitric oxide synthase activation; moreover, it has also been reported to act as a receptor for both SARS viruses. In the setting of the ongoing COVID-19 pandemic, the SARS–ACE2 interaction is highly debated with respect to both viral infectivity and usage/discontinuation of RAAS medication—ACE inhibitors (ACEi) and angiotensin-receptor blockers (ARBs)—in diagnosed or suspected SARS-CoV2 patients. Since ACE inhibitors and ARBs are largely prescribed in cardiovascular pathology, a better understanding of the interaction between SARS-CoV2 and RAAS is urgently needed. In this review, we will briefly discuss the SARS-CoV2 and ACE2 interaction and why the discontinuation of RAAS medication is unsafe for either diagnosed or suspected SARS-CoV2 patients.

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Could Anti‐Hypertensive Drug Therapy Affect the Clinical Prognosis of Hypertensive Patients With COVID‐19 Infection? Data From Centers of Southern Italy

Journal of the American Heart Association ◽

10.1161/jaha.120.016948 ◽

2020 ◽

Vol 9 (17) ◽

Cited By ~ 16

Author(s):

Celestino Sardu ◽

Paolo Maggi ◽

Vincenzo Messina ◽

Pasquale Iuliano ◽

Antonio Sardu ◽

...

Keyword(s):

Intensive Care Unit ◽

Mechanical Ventilation ◽

Angiotensin Converting Enzyme ◽

Enzyme Inhibitor ◽

Angiotensin Receptor Blockers ◽

Converting Enzyme ◽

Angiotensin Receptor ◽

Angiotensin Converting Enzyme 2 ◽

Receptor Blockers ◽

Worse Prognosis

BACKGROUND Coronavirus disease 2019 (COVID‐19) is the cause of a pandemic disease, with severe acute respiratory syndrome by binding target epithelial lung cells through angiotensin‐converting enzyme 2 in humans. Thus, patients with hypertension with COVID‐19 could have worse prognosis. Indeed, angiotensin‐converting enzyme inhibitors and/or angiotensin receptor blockers may interfere with angiotensin‐converting enzyme 2 expression/activity. Thus, patients with hypertension undergoing angiotensin‐converting enzyme inhibitor and/or angiotensin receptor blockers drug therapy may be at a higher risk of contracting a serious COVID‐19 infection and should be monitored. Moreover, in the present study we investigated the effects of angiotensin‐converting enzyme inhibitor versus angiotensin receptor blockers versus calcium channel blockers on clinical outcomes as mechanical ventilation, intensive care unit admissions, heart injury, and death in 62 patients with hypertension hospitalized for COVID‐19 infection. METHODS AND RESULTS The multicenter study was prospectively conducted at Department of Infectious Diseases of Sant'Anna Hospital of Caserta, and of University of Campania "Luigi Vanvitelli" of Naples, at Department of Advanced Surgical and Medical Sciences of University of Campania "Luigi Vanvitelli," Naples, and at General Medical Assistance Unit "FIMG," Naples, Italy. Lowest values of left ventricle ejection fraction predicted deaths (1.142, 1.008–1.294, P <0.05), while highest values of interleukin‐6 predicted the admission to intensive care unit (1.617, 1.094–2.389), mechanical ventilation (1.149, 1.082–1.219), heart injuries (1.367, 1.054–1.772), and deaths (4.742, 1.788–8.524). CONCLUSIONS Anti‐hypertensive drugs didn't affect the prognosis in patients with COVID‐19. Consequently, tailored anti‐inflammatory and immune therapies in addition to chronic antihypertensive therapy, could prevent a worse prognosis, as well as improve the clinical outcomes in patients with hypertension with COVID‐19 infection.

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Angiotensin-Converting Enzyme 2 and the Resolution of Inflammation: In Support of Continuation of Prescribed Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers

Mayo Clinic Proceedings ◽

10.1016/j.mayocp.2020.05.001 ◽

2020 ◽

Vol 95 (7) ◽

pp. 1552-1553

Author(s):

Felice L. Gersh

Keyword(s):

Angiotensin Converting Enzyme ◽

Enzyme Inhibitors ◽

Angiotensin Receptor Blockers ◽

Angiotensin Converting Enzyme Inhibitors ◽

Converting Enzyme ◽

Angiotensin Receptor ◽

Converting Enzyme Inhibitors ◽

Resolution Of Inflammation ◽

Angiotensin Converting Enzyme 2 ◽

Receptor Blockers

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Angiotensin-Converting Enzyme Inhibitor / Angiotensin II Receptor Blocker in COVID-19: a Double-edged Sword or a Myth

Nepalese Medical Journal ◽

10.3126/nmj.v3i1.28726 ◽

2020 ◽

Vol 3 (1) ◽

pp. 309-312

Author(s):

Kunal Bikram Shaha ◽

Ashok Adhikari ◽

Jung Rae Cho ◽

Bimal Pandey ◽

Yubaraj Sharma ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Angiotensin Converting Enzyme ◽

Enzyme Inhibitors ◽

Angiotensin Receptor Blockers ◽

Angiotensin Converting Enzyme Inhibitors ◽

Converting Enzyme ◽

Angiotensin Receptor ◽

Converting Enzyme Inhibitors ◽

Angiotensin Converting Enzyme 2 ◽

Receptor Blockers

Angiotensin-converting enzyme-2 receptor has been unearthed as a prime site of entry of Severe Acute Respiratory Syndrome Coronavirus 2 owing to its strong affinity towards spike protein of Severe Acute Respiratory Syndrome Coronavirus 2, resulting in down-regulation of Angiotensin-converting enzyme -2 receptors and hyperstimulation of Angiotensin-converting enzyme-1 pathway. This proposed theory has led to the birth of a new controversy regarding the use of Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in Coronavirus disease 2019 patients. A theory is against the use of Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, as it enhances the effect of Angiotensin-converting enzyme -2 pathway and upregulation of Angiotensin-converting enzyme -2 receptors resulting in a large number of internalizations of Severe Acute Respiratory Syndrome Coronavirus -2 into cells culminating into a high load of viremia with overwhelming infection and severity. The other theory considers Angiotensin-converting enzyme inhibitors / Angiotensin receptor blockers useful as it blocks deleterious Angiotensin-converting enzyme -1 pathway triggered by Severe Acute Respiratory Syndrome Coronavirus 2 and enhances Angiotensin-converting enzyme -2 receptor upregulation and activation of angiotensin-(1-7) leading to beneficial effects, i.e vasodilation, anti-apoptosis, anti-proliferative, & antifibrosis. Hence, Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers may prove beneficial in countering the Angiotensin-converting enzyme -1 mediated damage by Severe Acute Respiratory Syndrome Coronavirus 2. The recommendations by (European & American) societal guidelines still hold good of not discontinuing Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in COVID-19 patients as it is further supported by current evidence of large observational studies.

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