As the first and rate-limiting step, renin converts angiotensinogen, a precursor molecule, into the decapeptide AngI. AngI is subsequently converted into AngII by ACE, a zinc metalloprotease predominantly found in the endothelial cells of the lungs (3). Cathepsin and chymase are also capable of hydrolyzing AngI to AngII. AngII exerts opposing effects: vasoconstriction through its binding to AT₁R and vasodilation via AT₂R. AngII promotes aldosterone production in the adrenal gland zona glomerulosa by enhancing the function of the steroidogenic acute regulatory (StAR) protein and aldosterone synthase, and causes an increase in sodium retention and potassium expulsion, resulting in a rise in water retention and BP. Glutamyl aminopeptidase A (AP-A) cleaves the N-terminal aspartate residue from AngII, producing the heptapeptide AngIII, which is subsequently converted to the hexapeptide AngIV by alanyl aminopeptidase N (AP-N) through cleavage of the N-terminal arginine. AngIV can then be further metabolized into Ang-(3–7) by the action of carboxypeptidase P and prolyl oligopeptidase. Alternatively, AngII can be converted into a heptapeptide Ang-(1–7) by carboxypeptidase P and ACE2, an isoform of ACE (3). ACE2 also catalyzes the conversion of AngI to Ang-(1–9), which can then be converted into Ang-(1–7) by ACE or produced directly from AngI via neutral endopeptidase. A newly identified component of the RAAS is alamandine, which is formed either by decarboxylation of Ang-(1–7) or through ACE2-mediated cleavage of angiotensin A—derived from the decarboxylation of AngII (5). ACE, angiotensin-converting enzyme; ACE2, angiotensin-converting enzyme 2; AngI, angiotensin I; AngII, angiotensin II; AngIII, angiotensin III; AngIV, angiotensin IV; AT₁R, angiotensin II type 1 receptor; AT₂R, angiotensin II type 2 receptor.