Human sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y bioavailability

What is the purpose of sympathetic neuronal action potential (AP) discharge and recruitment patterns for human vascular regulation? This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. We used microneurography to record muscle sympathetic nerve activity and a continuous wavelet transform to detect sympathetic APs during a baseline condition and intravenous dexmedetomidine infusion (α₂-adrenergic agonist, 10-min loading infusion of 0.225 µg·kg^-1; maintenance infusion of 0.1-0.5 µg·kg·h^-1) in six healthy individuals (5 females, 27 ± 6 yr). Arterial blood samples provided NPY (enzyme-linked immunosorbent assay) and norepinephrine (liquid chromatography-tandem mass spectrometry) levels at baseline and the dexmedetomidine maintenance infusion. Linear mixed-model regressions assessed the relationships between AP discharge, recruitment, and neurotransmitter levels. Across baseline and the dexmedetomidine condition, NPY levels were positively related to mean arterial pressure (β = 1.63 [0.34], <i>P</i> = 0.002), total AP clusters (β = 0.90 [0.22], <i>P</i> = 0.005), and AP frequency (β = 0.11 [0.03], <i>P</i> = 0.003). Norepinephrine levels were not related to mean arterial pressure (β = 0.03 [0.02], <i>P</i> = 0.133) but were positively related to total AP clusters (β = 19.50 [7.07], <i>P</i> = 0.030) and AP frequency (β = 2.66 [0.81], <i>P</i> = 0.014). These data suggest that sympathetic neuronal discharge and recruitment patterns regulate NPY and norepinephrine bioavailability in healthy adults. As such, sympathetic neuronal firing strategies are important for human vascular regulation.<b>NEW & NOTEWORTHY</b> The purpose of sympathetic neuronal discharge and the recruitment of neuronal subpopulations for human circulatory homeostasis remains unknown. This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. Across baseline and an intravenous dexmedetomidine infusion (α₂-adrenergic agonist) sympathetic action potential (AP) frequency and total sympathetic AP clusters were associated with NPY bioavailability. This is the first study to report that sympathetic neuronal discharge and recruitment patterns regulate NPY bioavailability to support circulatory homeostasis in humans.