Divergent pathways for the angiotensin-(1-12) metabolism in the rat circulation and kidney

► Serum ACE processes Ang-(1-12) to Ang II through the generation of Ang I. ► Serum renin does not metabolize Ang-(1-12) to shorter angiotensin peptides. ► Rat, human and mouse neprilysin process Ang-(1-12) to Ang-(1-7) and Ang-(1-4). ► Kinetic modeling does not favor Ang-(1-12) as the immediate precursor to Ang I.