Understanding the role of nACE2 in neurogenic hypertension among COVID-19 patients

Hypertens Res. 2022 Feb;45(2):254-269. doi: 10.1038/s41440-021-00800-4. Epub 2021 Nov 30.


Currently, the third and fourth waves of the coronavirus disease -19 (COVID-19) pandemic are creating havoc in many parts of the world. Although vaccination programs have been launched in most countries, emerging new strains of the virus along with geographical variations are leading to varying success rates of the available vaccines. The presence of comorbidities such as diabetes, cardiovascular diseases and hypertension is responsible for increasing the severity of COVID-19 and, thus, the COVID-19 mortality rate. Angiotensin-converting enzyme 2 (ACE2), which is utilized by SARS-CoV-2 for entry into host cells, is widely expressed in the lungs, kidneys, testes, gut, adipose tissue, and brain. Infection within host cells mediates RAS overactivation, which leads to a decrease in the ACE2/ACE ratio, AT2R/AT1R ratio, and MasR/AT1R ratio. Such imbalances lead to the development of heightened inflammatory responses, such as cytokine storms, leading to post-COVID-19 complications and mortality. As the association of SARS-CoV-2 infection and hypertension remains unclear, this report provides an overview of the effects of SARS-CoV-2 infection on patients with hypertension. We discuss here the interaction of ACE2 with SARS-CoV-2, focusing on neuronal ACE2 (nACE2), and further shed light on the possible involvement of nACE2 in hypertension. SARS-CoV-2 enters the brain through neuronal ACE2 and spreads in various regions of the brain. The effect of viral binding to neuronal ACE2 in areas of the brain that regulate salt/water balance and blood pressure is also discussed in light of the neural regulation of hypertension in COVID-19.

Keywords: Brain.; COVID-19; Hypertension; Neuronal Angiotensin-Converting Enzyme 2; Renin-Angiotensin System; SARS-CoV-2:.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • COVID-19*
  • Humans
  • Hypertension*
  • Peptidyl-Dipeptidase A / metabolism
  • Renin-Angiotensin System
  • SARS-CoV-2


  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2