LAUSR

Exercise is a well-known sympathoexcitatory stimulus. However, muscle sympathetic nerve activity (MSNA) can decrease during the onset of muscle contraction. Yet, the underlying mechanisms and neurotransmitters involved in the sympathetic responses at the onset of exercise remain unknown. Herein, we tested the hypothesis that GABAA receptors may contribute to the MSNA responses at the onset of static handgrip in humans. Thirteen young, healthy individuals (4 females) performed 30 s of ischemic static handgrip at 30% of maximum volitional contraction before and following oral administration of either placebo or diazepam (10 mg), a benzodiazepine that enhances GABAA activity. MSNA (microneurography), beat-to-beat blood pressure (finger photopletysmography), heart rate (electrocardiogram) and stroke volume (ModelFlow) were continuously measured. Cardiac output (CO = stroke volume x heart rate) and total vascular conductance (TVC = CO / mean blood pressure) were subsequently calculated. At rest, MSNA was reduced while hemodynamic variables were unchanged after diazepam administration. Before diazepam, static handgrip elicited a significant decrease in MSNA burst frequency (∆-7±2 bursts/min, P<0.01 vs. baseline) and MSNA burst incidence (∆-16±2 bursts/100 heart beats, P<0.01 vs. baseline); however, these responses were attenuated following diazepam administration (∆-1±2 bursts/min and ∆-7±2 bursts/100 heart beats, respectively; P<0.01 vs. before diazepam). Diazepam did not affect the increases in heart rate, blood pressure, CO and TVC at the exercise onset. Importantly, the placebo had no effect on any variable at rest or exercise onset. These findings suggest that GABAA receptor activation modulates the MSNA responses at the onset of static exercise in young, healthy humans.