Abstract 18505: Endogenous Angiotensin-(1–7) Activity in the Rostral Ventrolateral Medulla Is Enhanced in Spontaneously Hypertensive Rats via Sympathetic Nerve Activity
Background: Ang-(1–7) is a peptide ligand for the Ang-(1–7)-Mas receptor, and mainly forms angiotensin (Ang) II through a newly identified enzyme, angiotensin-converting enzyme 2 (ACE2). Although Ang II and Ang-(1–7) have antagonizing effects on the vasculature, microinjections of Ang-(1–7) into the RVLM (brainstem vasomotor center) have been shown to increase arterial pressure (AP) in normotensive rats.
Hypothesis: The Ang-(1–7)-Mas axis in the RVLM contributes to the central mechanism of blood pressure regulation and hypertension.
Methods and Results: We microinjected Ang-(1–7) (100 pmol), Ang-(1–7)-Mas receptor antagonist (A-779: 100 pmol), or ACE2 inhibitor (DX600: 25 pmol) into the RVLM of anesthetized Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Unilateral microinjections of Ang-(1–7) increased AP more in SHR than in WKY (13.3±1.3 mmHg, n=7 vs. 6.6±0.8 mmHg, n=5; p<0.05). In contrast, bilateral microinjections of the A-779 decreased AP (−26.4±1.7 mmHg, n=5 vs. −13.7±0.8 mmHg, n=5; p<0.05) and renal sympathetic nerve activity (−17.4±2.0%, n=4 vs. −7.5±1.0%, n=4; p<0.05) more in SHR than in WKY. Moreover, bilateral microinjections of DX600 induced a greater decrease in AP in SHR than in WKY (−23.8±3.4 mmHg, n=4 vs. −6.9±1.5 mmHg, n=5; p<0.05). In contrast, an angiotensin type 1 receptor blocker reduced blood pressure in SHR, but did not in WKY. The pressor response to Ang-(1–7) was inhibited by the prior injection of A-779 in SHR and WKY (3.3±0.5 mmHg, n=3 vs. 1.1±1.0 mmHg, n=3). Expression levels of Mas receptor in the RVLM tended to be greater in SHR than those of WKY.
Conclusions: AP responses to microinjections of Ang-(1–7) and its receptor blocker into the RVLM are enhanced in SHR compared with WKY. Endogenous Ang-(1–7) in the RVLM may contribute to the maintenance of blood pressure and renal sympathetic nerve activity in SHR as well as in WKY.
- © 2010 by American Heart Association, Inc.