Role of catecholamine-induced activation of vagal afferent pathways in regulation of sympathoadrenal system activity: negative feedback loop of stress response.

Stress-induced activation of the hypothalamic-pituitary-adrenal axis and sympathoadrenal system is precisely regulated by well-documented negative feedback mechanisms. These include direct negative feedback effect of glucocorticoids on brain structures regulating the hypothalamic-pituitary-adrenal axis activity. However, since the blood-brain-barrier is impermeable to circulating catecholamines, the role of circulating epinephrine and norepinephrine in feedback regulation of the sympathoadrenal system activity is unclear. Here we show that vagal innervation of the adrenal medulla combined with the presence of β-adrenergic receptors on vagal sensory neurons, the epinephrine-induced activation of vagal afferents, and increased plasma epinephrine levels following subdiaphragmatic vagotomy indicate that sensory fibers of the vagus nerve participate in the monitoring of plasma and tissue catecholamine concentrations. Furthermore, it shows that signaling transmitted by vagal afferents regulates sympathoadrenal system activity at the level of the brain. Therefore, we propose that vagal sensory fibers, directly activated by epinephrine and norepinephrine, represent the afferent limb of a negative feedback loop that adjusts the activity of the sympathoadrenal system according to actual plasma and tissue catecholamine levels.