Analysis of taVNS effects on baroreflex sensitivity and autonomic nervous system regulation during head-up tilt test

Baroreflex dysfunction and autonomic imbalance are key pathophysiological features of hypertension, but current pharmacological approaches often fail to address these neural mechanisms. This study investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) enhances autonomic regulation during blood pressure perturbation. In a randomized, single-blind, sham-controlled, crossover design experiment, 32 normotensive adults received 60-min taVNS or sham condition. Blood pressure perturbation was induced with the head-up tilt test (supine–tilt–supine). Heart rate variability (HRV) was analyzed across all four phases (S-baseline, early-tilt, late-tilt, recovery), whereas baroreflex sensitivity (BRS) was analyzed only during the 10-minute tilt phase. taVNS significantly increased parasympathetic HRV parameters (SDNN, RMSSD, pNN30, pNN50, HF) across all phases. During tilt, BRS up- and down-slope values increased significantly, indicating enhanced inter-beat interval responsiveness to systolic pressure fluctuations. In contrast, the sham procedure yielded no consistent changes in HRV or significant BRS alterations during tilt. These findings suggest that taVNS augments vagal modulation and baroreflex responsiveness, not only at rest but also during orthostatic stress, supporting a physiological mechanism that is likely mediated by auricular branch of the vagus nerve– nucleus tractus solitarius pathways. Consequently, taVNS shows potential to modulate conditions involving autonomic dysregulation, such as hypertension, and further research involving patient cohorts and longitudinal study protocols is needed. Clinical Trial: The clinical trial described in this paper was registered at https://cris.nih.go.kr/cris/index/index.do under the registration number KCT0011752 (first trial registered 20/03/2026, retrospective registration).