Background: Angiotensin-II (Ang-II) interacts with the sympathetic nervous system at central nervous blood pressure regulating structures including the baroreflex. It is unknown whether prolonged BP elevation mediated by high Ang-II plasma levels could induce a persistent shift of the central nervous baroreflex setpoint, lasting beyond the short Ang-II plasmatic half time of few seconds, thereby consolidating elevated BP and / or increased SNA in healthy humans. Methods: In a blinded cross-over design Ang-II or placebo (saline) was infused for a 6-hour period in 12 resting normotensive students (6 males) raising BP to borderline hypertensive levels. Between 60-120 minutes after the infusion period muscle sympathetic nerve activity (MSNA) was assessed microneurographically, and correlated with oscillometric BP measurements and heart rate at supine rest (baseline) and during pharmacologic baroreceptor challenge. Results: Infusion of Ang-II increased BP to borderline-hypertensive levels, as intended whereas heart rate remained unaltered. At baroreflex assessment (i.e. 60-120 minutes after end of infusion period), systolic BP was significantly higher compared to placebo (8.4±3.1 mmHg; p<0.05), whereas diastolic values were near equal between conditions. Baseline MSNA was neither decreased nor increased and baroreflex sensitivity to vasoactive drug challenge was not altered. Conclusion: Our results show that elevation of Ang-II plasma levels over 6-hours was able to increase systolic but not diastolic BP far beyond blood-mediated Ang-II effects. MSNA or heart rate did not counter-regulate this BP elevation, indicating that Ang-II had sustainably reset the central nervous BP threshold of sympathetic baroreflex function to accept elevated BP input-signals without counter-regulatory response.