Angiotensin 1-7 in the rostro-ventrolateral medulla increases blood pressure and splanchnic sympathetic nerve activity in anesthetized rats

- Angiotensin 1-7 (ANG-(1-7)), a derivative of angiotensin I or II, increases blood pressure and sympathetic nervous system activity after injection into the RVLM.
- ANG-(1-7) stimulates glutamate and ATP release by binding to the Mas receptor, which is expressed only on astrocytes in the RVLM.
- The effects of glutamate within the RVLM may also depend in part on astrocytic release of glutamate and ATP.
- Astrocytes acts as spatial and temporal filters to modulate the direct neuronal effects of glutamate and the renin-angiotensin system.

Angiotensin 1-7 (ANG-(1-7)), a derivative of angiotensin I or II, is involved in the propagation of sympathetic output to the heart and vasculature, and the receptor for ANG-(1-7), the Mas receptor, is expressed on astrocytes in the rostral ventrolateral medulla (RVLM). We recorded blood pressure (BP) and splanchnic sympathetic nerve activity (SSNA) before and after focal injection of ANG-(1-7) into the RVLM of rats. Unilateral injection of ANG-(1-7) into the RVLM, acting through the Mas receptor, increased SSNA and BP, and glutamate receptor antagonists, CNQX and D-AP5, partially reduced the ANG-(1-7) effect. ATP is often co-released with glutamate, and blocking ATP with PPADS also reduced the pressor response to microinjection of ANG-(1-7) within the RVLM. The effects of ANG-(1-7) were blocked by the MAS receptor antagonist, A-779 (which had no consistent effect on blood pressure or sympathetic nerve activity when injected on its own). We conclude that astrocytes in the RVLM participate in central, angiotensin-dependent regulation of blood pressure and sympathetic nerve activity, and the Mas receptor, when activated by ANG-(1-7), elicits the release of the gliotransmitters, glutamate and ATP. These gliotransmitters then cause an increase in sympathetic nerve activity and blood pressure by interacting with AMPA/kainate and P2X receptors in the RVLM.