When activated by Ang II, this receptor results in the following physiological outcomes:

- vasoconstriction

- inflammation

- reabsorption of salts and water

- oxidative stress, accelerated aging and brain degeneration

- kidney failure

- heart disease

- apoptosis


Ang II type 1 receptors (AT1R)

A receptor that is activated by Ang II.  

Ang II type 2 receptors (AT2R)

ACE2 is a surface bound enzyme, but when mice neuro-2A cells were exposed to Ang II and AT1R was activated, ACE2 was removed from the surface of the cell and degraded by lysosomes.  This may be a relevant mechanism related to SARS-CoV-2 cell entry.  

Neuronal ACE2 Internalization in COVID-19

ACE2 is a homologue of ACE.  Both enzymes are carboxypeptidases, meaning they cleave amino acids from the c-terminal of the peptide.  However, these homologues cleave the amino acid sequences at different points which leads to their different products.  ACE2 has four main physiological roles:

- Regulating blood pressure via its role in the renin-angiotensin-aldosterone system (RAAS)

- Limiting the amount of ACE substrate by converting Ang I into Ang 1-9

- Degrading Ang II in order to minimize its harmful effects

- Forming Ang 1-7 in order to maximize its cardioprotective effects

Angiotensin-converting enzyme 2 (ACE2)

Ang II is the produce of Ang I being cleaved by ACE.  This molecule is considered biologically active because it can influence physiological outcomes by acting on either Ang II type 1 receptors (AT1R) or Ang type 2 (AT2R) receptors.  

Michigan State University

ACE, a homologue of ACE 2, converts Ang I into Ang II.  ACE increases the amount of Ang II, a vasoconstrictor, and decreases the amount of a vasodilator.  This consequently results in increased blood pressure.  A class of drugs called ACE inhibitors, which are used for treating symptoms such as high blood pressure, block the activity of ACE.  ACE is generally more expressed than its homologue ACE 2.  

Angiotensin-converting enzyme (ACE)

Patel, V. B., Zhong, J. C., Grant, M. B., & Oudit, G. Y. (2016). Role of the ACE2/angiotensin 1–7 axis of the renin–angiotensin system in heart failure. Circulation research, 118(8), 1313-1326.

Role of the ACE2/Angiotensin 1–7 axis of the Renin-Angiotensin System in Heart Failure

Angiotensin II (Ang II)

Because ACE and ACE2 are structurally similar, it was thought that existing ACE inhibitor (ACE-I) drugs could be used as a COVID-19 treatment by inhibiting ACE2 activity.  However, because the enzymatic binding sites of ACE and ACE2 are different, ACE-Is do not affect ACE2 activity.  Additionally, COVID-19 patients who took ACE-I drugs were more likely to experience more severe symptoms and had a higher mortality rate than those that didn't take them.  It is thought that ACE inhibition in the RAS may exacerbate the vulnerability of patients with hypertension, diabetes mellitus, or cardiovascular disease to SARS-CoV-2 infection or COVID-19 symptoms.

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