Fig. 3.

a Action of ACE and ACE2 enzymes in the KKK system. ACE degrades bradykinin, a vasodilator peptide acting mainly through BR2 receptors. This kinin can be also converted by kininase I into des-Arg9-bradykinin, which promotes vasoconstriction and pro-inflammatory effects upon interaction with BR1 receptors. ACE2 participates in the degradation of des-Arg9-bradykinin, a process eventually inhibited by SARS-CoV-2-induced ACE2 downregulation. b SARS-CoV-2-mediated imbalance in the KKK system with predominant pro-inflammatory effect of des-Arg9-bradykinin. c Age-related variations in the RAAS, KKK system and COX-2 and ACE D isoform as enhancers of the susceptibility of older adults to present severe COVID-19 symptoms