Role of the renin-angiotensin system in the development of severe COVID-19 in hypertensive patients

Abstract

A new form of severe acute respiratory syndrome (SARS) caused by SARS-CoV-2, called COVID-19, has become a global threat in 2020. The mortality rate from COVID-19 is high in hypertensive patients, making this association especially dangerous. There appears to be a consensus, despite the lack of experimental data, that angiotensin II (Ang II) is linked to the pathogenesis of COVID-19. This process may occur due to acquired deficiency of angiotensin-converting enzyme 2 (ACE2), resulting in reduced degradation of Ang II. Furthermore, Ang II has a critical role in the genesis and worsening of hypertension. In this context, the idea that that there is a surge in the level of Ang II with COVID-19 infection causing multiple organ injuries in hypertensive patients becomes attractive. However, the role of other components of the renin angiotensin system (RAS) in this scenario requires elucidation. The identification of other RAS components in COVID-19 hypertension may provide both diagnostic and therapeutic benefits. Here, we summarize the pathophysiologic contributions of different components of RAS in hypertension and their possible correlation with poor outcome observed in hypertensive patients with COVID-19.

Immediate and post-COVID complications of symptomatic and asymptomatic COVID-19 patients in Bangladesh: a cross-sectional retrospective study

“…We found that COVID-19 symptomatic (2.45%) patients were more experienced with new-onset hypertension than asymptomatic (1.41%) patients. Downregulation of ACE-2 enzymes results in the reduced degradation of angiotensin II (ANG II) (Mascolo et al, 2020;Silva-Aguiar et al, 2020). Furthermore, the imbalance of ANG II in Renin-angiotensin system (RAS) can lead to genesis and worsening of hypertension in COVID-19 patients (Li et al, 2020).…”

Thimet Oligopeptidase—A Classical Enzyme with New Function and New Form

“…Interestingly, Soria-Castro et al [105] recently reported that COVID-19 patients showed increased carboxypeptidase A3 (CPA3), which is also known for its function in converting angiotensin II to angiotensin 1-7 [81]. Another enzyme prolylcarboxypeptidase that can catalytically convert angiotensin II to angiotensin 1-7 may also be involved in COVID-19 pathophysiology [106]. Taken together, these findings suggest potential involvement of TOP or other endopeptidases and carboxypeptidases in the pathophysiology of COVID-19 infection is an area worthy of further investigation.…”

Angiotensin-converting enzyme 2 and COVID-19: patients, comorbidities, and therapies

“…Hypertension’s integrative role with other organs affects RAS systemically and locally, which is activated by distinct signals from differing physiologic and pathophysiologic conditions ( 171 , 172 ). Essential hypertension can be delineated into two groups based on plasma renin activity: those with low activity, and those with normal-to-high activity ( 173 ). Studies show that hypertension with high plasma renin activity relates to increased cardiovascular complications and vascular damage ( 173 – 175 ).…”

“…Essential hypertension can be delineated into two groups based on plasma renin activity: those with low activity, and those with normal-to-high activity ( 173 ). Studies show that hypertension with high plasma renin activity relates to increased cardiovascular complications and vascular damage ( 173 – 175 ). The deleterious effects may destroy ACE2 mRNA and protein activity in tissue, as hypertensive clinical and experimental models show, primarily in the kidneys and heart and thus depict hypertensive progression decreasing local ACE2 activity ( 97 , 176 – 180 ).…”

“…Large clinical studies are needed to clarify ACE2’s role in essential and secondary hypertension, acute and chronic hypertension, and hypertensive disease progression. Determination of plasma renin activity in both hypertensive and nonhypertensive COVID-19 patients may also indicate prognosis and treatment decisions ( 173 ).…”