Cardiovascular and sympathetic neural responses during acute vagus nerve stimulation and subsequent static handgrip exercise in healthy adults☆

Purpose: This study aimed to investigate cardiovascular and sympathetic neural responses during acute cervical non-invasive vagus nerve stimulation (nVNS) and subsequent static handgrip (SHG) exercise with post-exercise circulatory occlusion (PECO) in healthy humans. Methods: Ten healthy adults (5 men and 5 women, 33 f 9 [standard deviation] yrs) participated in this doubleblinded, randomized, crossover study. Each participant was studied twice on two separate days, with approximately 4 weeks apart: once during the actual cervical nVNS and once during sham stimulation for 4 min each. Mean arterial pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were measured during nVNS and sham stimulation. In addition, participants performed SHG at 40 % of maximal voluntary contraction until fatigue, followed by 2-min PECO to isolate muscle metaboreflex activation before and after each stimulation. Results: During both nVNS and sham stimulation, HR decreased (triangle- 4 f 4 and triangle- 4 f 5 bpm; both P < 0.001), and MSNA increased (triangle 4 f 6 and triangle 2 f 3 bursts/min; both P < 0.001) in all participants, although MAP remained unchanged (P = 0.312). However, these responses did not differ between nVNS and sham stimulation (all P > 0.05). Additionally, there were no differences in cardiovascular and MSNA responses to fatiguing SHG and PECO between stimulations (all P > 0.05). Conclusion: Compared to the sham condition, cervical nVNS had no significant impact on cardiovascular variables and MSNA during acute stimulation, nor on the responses to SHG or PECO. These findings suggest that cervical nVNS has no or minimal acute effect on sympathetic neural (re)activity in healthy adults.