Silencing of Nox2 and Nox4 in the subfornical organ prevents renal but not aortic T cell infiltration during angiotensin II‐induced hypertension (874.9)

Reactive oxygen species (ROS) in the SFO are crucial for Ang II HTN and have been linked to aortic T cell activation. Signals from the SFO regulate renal sympathetic nerve activity (RSNA). Increased RSNA contributes to renal T cell activation. Here we compared the effects of silencing the two NADPH oxidase (Nox) isoforms (Nox2, Nox4) found in the SFO on aortic and renal T cell activation during Ang II HTN. We targeted the SFO of C57Bl/6 mice with adenoviruses encoding siRNAs directed selectively against Nox2 and Nox4 (AdsiNox2 + AdsiNox4). One week later osmotic minipumps were implanted to infuse Ang II (600 ng/kg/min) for 14 days. Silencing of both Nox2 and Nox4 significantly reduced SFO ROS and blunted Ang II‐HTN. Flow Cytometry revealed that despite normal arterial pressure, silencing of Nox2 and Nox4 in the SFO did not prevent aortic T cell infiltration in response to Ang II (AdLacZ Veh: 0.2 ± 0.06 x 10 4 , Ang II: 5.6 ± 2.0 x 10 4 ; AdsiNox2+AdsiNox4 Veh: 0.09 ± 0.02 x 10 4 , Ang II: 9.1 ± 3.8 x 10 4 cells/aorta; n=5‐8, p<0.05 vs AdLacZ). In contrast, renal T cell infiltration was blunted in these animals (AdLacZ Veh: 0.2 ± 0.05 x 10 4 , Ang II: 2.1 ± 0.4 x 10 4 ; AdsiNox2+AdsiNox4 Veh: 0.4 ± 0.1 x 10 4 , Ang II: 0.4 ± 0.9 x 10 4 ; n=5, p<0.05). These findings demonstrate that Nox‐derived ROS in the SFO are important for renal T cell infiltration and kidney inflammation, and suggest that this may be important for the development of Ang II HTN. Grant Funding Source : 12SDG9160019, HL63887, HL96571, HL84207