Slow‐pressor angiotensin II (AngII)‐dependent hypertension (HTN) requires prostaglandin E2 (PGE2) type 1 receptors (EP1R) and superoxide (O2·‐) signaling

Abstract

Oxidant signaling in the subfornical organ (SFO), a primary CNS sensor for blood‐borne AngII, plays a causative role in slow‐pressor AngII‐dependent HTN. PGE2 and EP1R are also implicated in AngII‐induced vasopressor effects, but it is not known if they act in brain or other organs. Here we hypothesized that AngII HTN is mediated by PGE2 signaling in the brain and that blocking EP1R in the SFO would prevent AngII HTN by inhibiting O2−. production. C57BL/6 mice were implanted with telemeters for mean arterial pressure (MAP) recordings, osmominipumps for 2 wks AngII infusion (600 ng/kg/min), and ICV cannulae for infusion of the selective EP1R antagonist SC‐51089 (6 μg/h) or saline (0.25 μl/h) for 2 wks. Ang‐II infusion induced HTN in mice receiving ICV saline (baseline: MAP=101±5; day 12 AngII: MAP=129±5 mmHg, n=4, p<0.05). This HTN was abolished in mice receiving ICV SC‐51089 (baseline: MAP=100±2; day 12 AngII: MAP=101±7 mmHg, n=4). In mice treated with ICV saline, AngII infusion also produced a 1.9±0.4 fold increase in O2−. production in the SFO as measured by dihydroethidium, which was completely prevented in mice treated with ICV SC‐51089 (fold change=0.9±0.2; p>0.05). These data suggest that EP1R activation in the CNS is critical in slow pressor AngII‐induced HTN and implicate O2−. in the SFO in this effect. Supported by HL063887, HL084624, AHA 0540114N.