Abstract P220: Angiotensin II Dependent And Independent Pressor Effect Of Ang-(1-12)

Background: Ang-(1-12) serves as a functional substrate for the formation of Ang II in the blood and tissues. It remains unknown whether the hypertensive effect of Ang-(1-12) is solely caused by Ang II formation or whether the peptide itself exerts a pressor effect by binding to the AT1-receptor or a yet-to-be-identified receptor subtype. Here we examined the possibility of Ang II independent pressor effects of Ang-(1-12). Methods: Anesthetized male c57bl6 mice were injected with Ang II or Ang-(1-12) (0.2 μg/g BW) and the systolic blood pressure (SBP) was measured continuously for 15 minutes. To evaluate whether Ang-(1–12) vasoconstrictor activity is due to its processing into Ang II, mice were preinjected with Telmisartan or Lisinopril before Ang-(1-12) injection. We further assessed the effect of recombinant (r) ACE2 as a way to augment Ang II metabolism and therefore unravel Ang II independent pressor effects of Ang-(1-12). Results: Ang-(1-12) infusion led to a peak increase in SBP almost as high as Ang II (145 ±24 mmHg vs. 160±26 mmHg, respectively). The pressor effect of Ang-(1-12) was completely abolished by either Telmisartan or Lisinopril (103±11 mmHg and 98±12 mmHg, respectively). rACE2 prevented the sustained rise in SBP induced by Ang II (Fig. 1), but it did not affect the pressor effect of Ang-(1-12) (Fig. 1). Conclusions: Ang-(1–12) hypertensive effect is blocked by RAS blockade consistent with an action dependent on Ang II formation and coupling to AT-1 receptors. In contrast, Ang-(1–12) pressor activity is not modified when Ang II is rapidly metabolized by rACE2. These data suggest a vasoactive action of Ang-(1–12) that is, in part, independent of its conversion into Ang II.