Sleep-stage-specific regulation of plasma catecholamine concentration

The catecholaminergic system is critically involved in the regulation of sleep, wake and arousal states. In the central nervous system, sleep is characterized by low levels of norepinephrine compared to wakefulness, reaching minimum levels during rapid eye movement (REM) sleep. It is not yet clear whether blood catecholamine concentrations (as a measure of sympathetic activity in the body periphery) show a similar sleep stage-dependent decline or depend mainly on a circadian rhythm. Here, we show that during sleep in humans, plasma concentrations of norepinephrine (NE) and epinephrine (E) exhibit a progressive decline associated with the stage of sleep, irrespective of the circadian time of sleep. In a within-subject design, healthy men (n=12) slept for 7h either during daytime or nighttime. Sleep was framed by 3-h periods of wakefulness during which subjects rested in a supine position. We sampled blood at a fast rate (1/10 min) and monitored blood pressure and heart rate continuously. Plasma catecholamine concentrations distinctly declined in a linear fashion as sleep deepened, reaching a minimum during REM sleep both during daytime and nighttime sleep. Diverging from this pattern, cardiovascular parameters indicated lowest blood pressure and heart rate during slow wave sleep (SWS), whereas during REM sleep activity increased almost to waking levels. Because the changes observed here in human blood catecholamine levels closely mimic the changes in brain catecholamine activity, as well-documented in animals, we suggest that the organism's overall catecholamine activity during sleep is well represented by measures of plasma catecholamine concentrations.