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 The Potential Role of ACEi and ARBs in COVID-19; A Perpsective

2020 ◽  
Author(s):  
Ahmad Hammad Hassan
Keyword(s):  
Lung Injury ◽  
Angiotensin Converting Enzyme ◽  
Enzyme Inhibitors ◽  
Angiotensin Receptor Blockers ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Converting Enzyme Inhibitors ◽  
Upper Respiratory Infection ◽  
Cardiac Illness

COVID-19 pandemic has caused significant morbidity and mortality around the world. The disease severity ranges from mild upper respiratory infection to severe lower respiratory and cardiac illness. Acute respiratory distress syndrome (ARDS) is the most serious complication and results in diffuse inflammatory alveolar damage, respiratory failure, and death. Components of the Renin-Angiotensin-Aldosterone-System (RAAS) are involved in an inflammatory reaction in the lungs. Various studies have shown that blocking RAAS peptides in the lungs especially angiotensin-converting enzyme (ACE) and type-1 angiotensin receptor (ATR1) reduces lung injury, improves respiratory function, and is associated with better clinical outcomes in the COVID-19 patients. We suggest that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) – drugs that block RAAS peptides – be considered for a repurposed use in COVID-19 induced lung injury.

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.

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