Possible connection
between the pathophysiology of Hypertension
and SARS-CoV-2 infection. (A) ACE2/Ang I–VII/Mas axis and the
renin-angiotensin system (RAS). Angiotensinogen is transformed to
Ang-I by the protease renin, which is then converted to Ang-II by
the ACE. Vasoconstriction, hypertrophy, fibrosis, proliferation, inflammation,
and oxidative stress can be caused by Ang-II following binding to
the AT1 receptor. Ang-I and Ang-II can be converted to Ang I–IX
and Ang I–VII respectively by ACE2. Vasodilatation, vascular
protection, anti-fibrosis, anti-proliferation, and anti-inflammation
are effects of Ang I–VII binding to the Mas receptor. (B) When
SARS-CoV-2 binds to ACE2, the virus is internalized with the receptor,
and ACE2 is removed via ADAM17. Reduced ACE2 availability causes a
decrease in the levels of Ang I–VII, I–IX, and Ang-II
degradation, as well as increased AT1 receptor activation, facilitating
HTN, ARDS, and fibrosis. (C) Infection with SARS-CoV-2 and therapy
with ACEi/ARB. After SARS-CoV-2 binding, ACE2 is upregulated by ACEi
and ARB, and free ACE2 persists. Ang I–VII, a favorable metabolite
of Ang II, is still destroyed by ACE2, although the AT1 receptor is
less activated than Mas receptor-activated through increased levels
of Ang I–VII and I–IX resulting in vasodilatation, hypotension,
and antifibrotic activity. ARB prevents Ang II binding on the AT1
receptor, while ACE decreases Ang II production, resulting in decreased
AT1 receptor activation and sustained interaction with ACE2, preventing
ACE2 internalization.