Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2021 Mar 15;72(6):1105-1107.
doi: 10.1093/cid/ciaa818.

COVID-19 and the Renin-Angiotensin-Aldosterone System

George O A Naik  1
Affiliations
Comment

COVID-19 and the Renin-Angiotensin-Aldosterone System

George O A Naik. Clin Infect Dis. .
No abstract available

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Flow diagram showing the renin-angiotensin-aldosterone system (RAAS) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and points of RAAS drug blockade (A) and implications of angiotensin-converting enzyme 2 (ACE2) perturbations on directly affected angiotensins (Angs) (B). Changes in ACE2 expression would impact the beneficial, deleterious, and other components of the RAAS. Physiologically, the RAAS maintains blood pressure and body water balance. ACE2 is downregulated by SARS-CoV-2 infection and renin inhibition (RI), and upregulated by angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs). Renin is secreted from the kidney, which transforms angiotensinogen to Ang I, the rate-limiting step. Circulating renin can also bind to (pro)renin receptor (PRR) with likely activation of the local tissue renin-angiotensin system throughout the body. Ang I is converted to Ang II by ACE and by a second enzyme, chymase. ACE also converts bradykinin (1–9) to bradykinin (1–7) [Bk (1–7)]. Ang II is further transformed to Ang III, Ang IV, and Ang V. A negative feedback loop controls Ang II concentration changes with renin secretion that responds in the opposite direction. Ang II stimulates the release of aldosterone. However, excessive Ang II is deleterious and is associated with hypertension, congestive heart failure, and chronic kidney disease. ACE2 transforms Ang I and Ang II, that is, Ang I to Ang (1–9), and Ang II to Ang (1–7). Ang (1–9) and Ang (1–7) have protective effects balancing the deleterious Ang II, when in excess.
See this image and copyright information in PMC

Comment on

References

    1. Hanff TC, Harhay MO, Brown TS, Cohen JB, Mohareb AM. Is there an association between COVID-19 mortality and the renin-angiotensin system—a call for epidemiologic investigations [manuscript published online ahead of print 26 March 2020]. Clin Infect Dis 2020. doi:10.1093/cid/ciaa329. - PMC - PubMed
    1. Keidar S, Gamliel-Lazarovich A, Kaplan M, et al. . Mineralocorticoid receptor blocker increases angiotensin-converting enzyme 2 activity in congestive heart failure patients. Circ Res 2005; 97:946–53. - PubMed
    1. Chen J, Jiang Q, Xia X, et al. . Individual variation of the SARS-CoV2 receptor ACE2 gene expression and regulation. Preprints [Preprint]. Posted 12 March 2020:2020030191 Available at: https://www.preprints.org/manuscript/202003.0191/v1. Accessed 23 June 2020.
    1. Hamming I, Timens W, Bulthuis M, Lely A, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004; 203:631–7. - PMC - PubMed
    1. Bonow RO, Fonarow GC, O’Gara PT, Yancy CW. Association of coronavirus disease 2019 (COVID-19) with myocardial injury and mortality [manuscript published online ahead of print 27 March 2020]. JAMA Cardiol 2020. doi:10.1001/jamacardio.2020.1105. - DOI - PubMed

Substances