New Viral Diseases and New Possible Remedies by Means of the Pharmacology of the Renin-Angiotensin System

Figure 1

Diagram depicting pathways of synthesis and degradation of angiotensins in classical and nonclassical local/tissue RAS, with respective receptors for each bioactive peptide. ACE: angiotensin-converting enzyme; ACE2: angiotensin-converting enzyme type 2; AT_1-2-4Rs: angiotensin type 1-2-4 receptors; MasR: Mas receptor; MRGD: Mas-related G protein-coupled receptor member D; PCP: prolyl carboxypeptidase; PEP: prolyl endopeptidase. The main degradative pathway for Ang II in normal humans is through the sequential actions of plasma aminopeptidases A and N, not through ACE2; serine endopeptidase chymase, in the heart, renal tubules, and ubiquitous mast cells, converts Ang I into Ang II as efficiently as ACE does in the vascular endothelium; Zn-metalloendopeptidase neprilysin cleaves angiotensin I into Ang1-7. Neprilysin, based on the occasional substrate available, generates Ang1-7 from Ang I but may metabolize Ang1-7 to form Ang1-4.