Angiotensin (1–7) and Mas receptor activation inhibits Aldosterone induced ROS inflammatory responses in neurons of the paraventricular nucleus (PVN).

Abstract

It is now well recognized that the renin angiotensin system includes two separate enzymatic pathways that provide a physiological counterbalance of two related peptides acting at distinct receptors. The well described ACE ‐AngII‐AT1R system is thought to be physiologically opposed and balanced by the ACE2‐Ang‐(1–7)‐Mas receptor system. In the brain and other tissues, Ang II activation of AT1 receptors increases ROS related inflammation while Ang (1–7) and Mas receptor activation decrease ROS and inflammation. The present study investigated the effects of Ang (1–7) aldosterone (ALDO) induced increases in ROS production in PVN cells in vitro. PVN neurons were isolated from 22 day old female SD rats, dissociated and cultured on round coverslips and maintained in HBSS media for at least 48 hours prior to visualization by confocal microscopy. All cells were preincubated in 10nM ALDO for 48 hours and then 1.0 μM Ang (1–7) or 1.0 μM Ang (1–7) + 10.0 μM A779 for 2 hours prior to testing with acute 1.0 μM Aldo. To measure ROS, changes in the ethidium fluorescence were measured which is directly proportional to the oxidation of dihydroethidium (DHE) by ROS. The cells were loaded with DHE (20 μM) added to the cell culture media for 1h and then placed in a chamber for microscopic visualization of fluorescence. Perfusion with 1.0 μM ALDO increased ROS (Δ=113.4±28%) in the PVN neurons. In cells preincubated in Ang (1–7), ALDO increase in ROS was significantly inhibited (Δ=6.4±27%). Preincubation in Ang (1–7) + A779, restored the ALDO increase in ROS (Δ=105.9±9%). These results suggest that Ang (1–7) can inhibit ROS inflammatory effects of ALDO and this effect involves Ang (1–7) activation of the Mas receptor. (Supported by: HL‐14388, HL‐98207, and MH‐80241).