Fig. 1

Simplified overview of the renin angiotensin system (RAS). Angiotensinogen is cleaved by renin generating Angiotensin I (Ang I) which is then formed into Angiotensin II (Ang II) via the actions of angiotensin converting enzyme (ACE). Ang II preferentially binds to Angiotensin II type I receptor (AT₁R) (‘classical axis’) inducing vasoconstriction, inflammation, oxidative stress, apoptosis and cell proliferation. Ang II can also activate the Angiotensin II type II (AT₂R) and is metabolised by angiotensin converting enzyme 2 (ACE2) to generate Angiotensin-(1–7). Ang-(1–7) activates the Mas receptor (MasR). Ang-(1–7) can be formed by the actions of ACE or neprilysin (NEP) on Angiotensin-(1–9) or Angiotensin I. AT₂R and ACE2/Ang-(1–7)/MasR form the ‘alternative axis’ and its activation is thought to counteract the detrimental effects induced by AT₁R by leading to vasodilation, angiogenesis and preventing inflammation, oxidative stress and apoptosis