RAS and ACE2/Ang1-7/Mas Axis Regulation
Angiotensinogen is converted to angiotensin I (Ang I) via renin. Ang I is converted to Ang II via angiotensin-converting enzyme (ACE), which also hydrolyzes bradykinin into its inactive metabolites, promoting inflammation. The pro-inflammatory effects of Ang II are mediated by Ang II type I receptor (AT1), which stimulates aldosterone secretion from the adrenal medulla and antidiuretic hormone from the posterior pituitary. Aldosterone decreases membrane ACE2 expression. Endothelin-1 inhibits angiotensin 1-7 (Ang1-7) via extracellular signal-regulated kinase (ERK)1/ERK2 pathways. Ang II, under favorable conditions (dashed line), can be converted to Ang1-7 via ACE2, whose counter regulatory effects are mediated by the Mas receptor. Ang1-7 can also be formed via conversion of Ang I to an intermediate Ang1-9 or directly via zinc metallopeptidase neprilysin/prolyl endopeptidase (PEP). RAS = renin-angiotensin system.