Abstract 604.

Although angiotensin-(1-12) [Ang-(1-12)] is recognized as an alternate precursor for AngII, the biochemical pathways by which the substrate is released fromangiotensinogen (Aogen) are not yet described.We examined the role of renin on Ang-(1-12) formation from synthetic icosapeptide[Ang-(1-20)] in the systemic and coronary circulation of Wistar Kyoto rats(WKY). In experiment 1, rats underwent bilateralnephrectomy (BNX) or sham operation.After 48 hours, rats were assigned to sham+saline, sham+Ang-(1-20), orBNX+Ang-(1-20). Ang-(1-20) (20 nmol/kg/min)or saline was infused for 15 minutes. Atthe end of the study blood was collected for measuring Ang-(1-12), Ang I andAng II by RIA. Ang-(1-20) infusion increasedarterial pressure in both sham and BNX compared to sham+saline (P<0.001). Plasma Ang-(1-12), Ang I, and Ang II were significantlyhigher in sham+Ang-(1-20) compared to sham+saline. BNX+Ang-(1-20) showed significant increase inAng I and a tendency for augmented Ang-(1-12) and Ang II compared to sham+saline(Figure). In experiment 2, the hearts extractedfrom WKY were mounted on Langendorff apparatus.After recovery, 10 nmol or 100 nmol of Ang-(1-20), or 100 nmol ofAng-(1-20) with WFML-1 (a rat renin inhibitor) were perfused in the coronarycirculation. Buffer was recirculatedafter addition of Ang-(1-20) and WFML-1.Perfusate was collected at 0, 5, 15, 30, and 60 min for measurement of angiotensinsby RIA. The 100 nmol of Ang-(1-20)increase Ang-(1-12), Ang I, and Ang II compared to 10 nmol both in the absenceand in the presence of WFML-1 (Figure).We conclude that Ang-(1-12) is cleaved from Aogen by an enzyme that isnot renin in both systemic and coronary circulation. [ABSTRACT FROM AUTHOR]