Background: Previous studies report conflicting relationships between changes in blood pressure (BP), muscle sympathetic nerve activity (MSNA) and sympathetic baroreflex sensitivity (BRS) following renal denervation (RDN)1-4. The mechanisms underlying the anti-hypertensive effect of RDN remain unclear. Methods: We investigated changes in office BP, MSNA and BRS following RDN. Patients were assessed at 0, 1, 3, 6 and 12 months with measurement of MSNA (peroneal microneurography) and beat-to-beat BP (Finapres) over 5-10 min. Diastolic (D)BP readings were collated into 1 mmHg bins and the percentage of cardiac cycles containing an MSNA burst was calculated. The weighted linear fit to these data yields BRS5. Data analysed with ANOVA/Friedman test with Bonferroni/Dunn’s multiple comparison tests post hoc, and Pearson correlation, and presented as mean ± SEM. Results: 13 patients (8 men), aged 52±3 years, office BP 193±5/106±7 mmHg, taking 5±0.4 antihypertensives underwent RDN (10.8 ± 0.5 ablations). Mean baseline MSNA 60±6 bursts/100heartbeats and BRS -1.4±0.3 %/mmHg. Systolic (S)BP reduced post RDN (see Figure, p=0.006: 1 month, n=12, -15±9/-6±7 mmHg; 3 months, n=10, -21±10/8±7 mmHg; 6 months, n=13, -18±11 mmHg; 12 months, n=10, -30±12 mmHg). There was no change in MSNA or BRS (p=0.72 and p=0.63 respectively). At 1 and 6 months post RDN, those with a higher baseline SBP had a greater reduction in SBP (R=-0.68, p=0.01; R=-0.69, p=0.008), but there was no correlation between baseline MSNA and the change in SBP. There was a trend towards a positive correlation between baseline BRS and change in SBP at six months (R=0.52, p=0.07). Contrary to previous findings, those with a higher baseline SBP had lower MSNA at baseline (R=-0.67, p=0.01), this is likely because within this small cohort those with the highest baseline SBP were younger females with lower MSNA. 62% (8/13) patients responded to RDN with a ≥10 mmHg reduction in SBP at 6 months. Amongst these responders, BRS showed a strong trend towards a temporal pattern (p=0.06), increasing at 1 month and then returning to (at least) baseline levels by 12 months post RDN (see Figure), however, there was no change in MSNA (p=0.25). Conclusion: Patients who respond to RDN appear to have a short-term increase in BRS which regresses by 12 months. In contrast, the reduction in SBP post RDN is progressive and sustained, suggesting that temporary baroreflex modulation may be sufficient to reset BP to a lower operating level, although this is independent of MSNA, perhaps indicating post-junctional remodelling. These pilot data provide important insights into the autonomic mechanisms underlying RDN and will assist in directing future research.