Angiotensinogen metabolism in rat aorta: robust formation of proangiotensin-12

Renin-angiotensin system (RAS) plays important role in the regulation of vessel wall homeostasis. Proangiotensin-12 (proAng-12, Ang-(1-12)) is a newly characterized metabolite of angiotensinogen, formed in array of organs of rats, which may serve as an alternate substrate for local angiotensin production, by-passing the traditional renin-dependent conversion of angiotensinogen to angiotensin I. In this work using LC/MS method we identified proAng-12 as a main product of angiotensinogen metabolism ex vivo, in organ-bath of rat aortic tissue. In this setting, proAng-12 appeared to be not only prevalent metabolite of angiotensinogen, but also served as a substrate for generation of Ang I and subsequently, Ang II. The functional significance of this surprising finding requires further investigation.