Regulation of a novel angiotensin II precursor, proangiotensin-12, in the tissues by blockade of the renin–angiotensin system

Intracrine angiotensin II functions originate from noncanonical pathways in the human heart

“…Although renin is not necessary for Ang-(1-12) processing, studies by our laboratory (2, 3, 5, 92) and others (19,96,97,(107)(108)(109)116) demonstrated that Ang-(1-12) hydrolysis to Ang I and Ang II is achieved primarily through the proteolytic activities of ACE and chymase. Additional studies implicate the existence of alternate Ang-(1-12) processing in renal and vascular tissues, whereby neprilysin yields direct formation of Ang-(1-7) in rat renal cortical membranes (154) and carboxypeptidases A2 (cathepsin A) cleaves Ang-(1-12) into Ang I in rat mesenteric arteries (106) (Fig.…”