Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: potential allies in the COVID-19 pandemic instead of a threat?

Clin Sci (Lond). 2021 Apr 30;135(8):1009-1014. doi: 10.1042/CS20210182.

Abstract

Angiotensin-converting enzyme 2 (ACE2) is the leading player of the protective renin-angiotensin system (RAS) pathway but also the entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RAS inhibitors seemed to interfere with the ACE2 receptor, and their safety was addressed in COVID-19 patients. Pedrosa et al. (Clin. Sci. (Lond.) (2021), 135, 465-481) showed in rats that captopril and candesartan up-regulated ACE2 expression and the protective RAS pathway in lung tissue. In culture of pneumocytes, the captopril/candesartan-induced ACE2 up-regulation was associated with inhibition of ADAM17 activity, counterbalancing increased ACE2 expression, which was associated with reduced SARS-CoV-2 spike protein entry. If confirmed in humans, these results could become the pathophysiological background for justifying RAS inhibitors as cornerstone cardiovascular protectives even during COVID-19 pandemic.

Keywords: ACE2; ADAM17; COVID-19; angiotensin II type 1 receptor blocker; angiotensin-converting enzyme inhibitor.

Publication types

  • Comment

MeSH terms

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors* / pharmacology
  • Animals
  • Benzimidazoles
  • Biphenyl Compounds
  • COVID-19*
  • Captopril / pharmacology
  • Humans
  • Pandemics
  • Peptidyl-Dipeptidase A / metabolism
  • Rats
  • Renin-Angiotensin System
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus
  • Tetrazoles

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Benzimidazoles
  • Biphenyl Compounds
  • Spike Glycoprotein, Coronavirus
  • Tetrazoles
  • spike protein, SARS-CoV-2
  • Captopril
  • Peptidyl-Dipeptidase A
  • candesartan