Abstract
Increased PRR expression in the NTS of SHR, coupled with the evidence on role of the brain inflammation in cardiovascular functions, has led us to hypothesize that the NTS PRR may play a part in blood pressure (BP) regulation by modulation of the brain inflammatory pathways. Acute NTS injections of renin (0.02–2 pmol) resulted in a significantly greater dose‐dependent decrease in systolic BP (ΔSBP; −12±5 to −32±5 mmHg) and heart rate (ΔHR; −13±7 to −40±10 bpm) in the SHR compared to the WKY rats (ΔSBP: −3±1 to−8±4 mmHg; ΔHR: −2±4 to −12±7 bpm). These effects were not blocked by the AT1R or AT2R blocker. Consistent with this, chronic PRR knockdown with AAV2‐PRR‐shRNA in the SHR NTS caused an increase in mean arterial pressure (shRNA: 173±5; Control: 151±6 mmHg), and decreases in baroreflex bradycardia (shRNA: 0.26±0.04; Control: 0.44±0.04) and parasympathetic tone (shRNA: 31±4; Control: 49±6). This was accompanied by a decrease in the inflammatory markers TNFa, IL6 and Ccl5, and their transcription factors, NF‐κB and AP‐1. Finally, PRR activation in the SHR brain neuronal cultures activated NF‐κB, and increased the mRNA of IL1β (250 fold), TNFα (32 fold), IL6 (35 fold) and Ccl5 (12 fold) in an NF‐κB‐ and AP1‐dependent, but AT1R/AT2R‐independent manner. Therefore, the NTS PRR mediates Ang II‐independent antihypertensive effects by stimulation of NF‐κB/AP‐1/cytokine signaling (AHA 11SDG7420029)
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