Abstract 604: Renin Independent Ang-(1-12) Production in both the Systemic and Coronary Circulation
Although angiotensin-(1-12) [Ang-(1-12)] is recognized as an alternate precursor for Ang
II, the biochemical pathways by which the substrate is released from
angiotensinogen (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 bilateral
nephrectomy (BNX) or sham operation.
After 48 hours, rats were assigned to sham+saline, sham+Ang-(1-20), or
BNX+Ang-(1-20). Ang-(1-20) (20 nmol/kg/min)
or saline was infused for 15 minutes. At
the end of the study blood was collected for measuring Ang-(1-12), Ang I and
Ang II by RIA. Ang-(1-20) infusion increased
arterial pressure in both sham and BNX compared to sham+saline (P<0.001). Plasma Ang-(1-12), Ang I, and Ang II were significantly
higher in sham+Ang-(1-20) compared to sham+saline. BNX+Ang-(1-20) showed significant increase in
Ang I and a tendency for augmented Ang-(1-12) and Ang II compared to sham+saline
(Figure). In experiment 2, the hearts extracted
from WKY were mounted on Langendorff apparatus.
After recovery, 10 nmol or 100 nmol of Ang-(1-20), or 100 nmol of
Ang-(1-20) with WFML-1 (a rat renin inhibitor) were perfused in the coronary
circulation. Buffer was recirculated
after addition of Ang-(1-20) and WFML-1.
Perfusate was collected at 0, 5, 15, 30, and 60 min for measurement of angiotensins
by RIA. The 100 nmol of Ang-(1-20)
increase Ang-(1-12), Ang I, and Ang II compared to 10 nmol both in the absence
and in the presence of WFML-1 (Figure).
We conclude that Ang-(1-12) is cleaved from Aogen by an enzyme that is
not renin in both systemic and coronary circulation.
- © 2013 by American Heart Association, Inc.