Waking Levels Research Articles

Effects of sub‐anesthetic sevoflurane on cardiorespiratory responses to severe arterial hypoxia in the rabbit (709.4)

Volatile anesthetics may alter reflexes to hypoxia through actions at the carotid body chemoreceptors. The effects of sevoflurane (Sev) in sub‐anesthetic concentrations on integrated chemoreflex control during hypoxia are unknown. The cardiorespiratory responses to end‐tidal Sev (0.18%, 0.37% or 1.86%) were studied in 7 rabbits. Ventilation (VE), tidal volume (VT), respiratory rate (f), heart rate (HR) and arterial pressure (AP) were measured in awake rabbits breathing room air, then 5 minutes of hypoxia (PaO2 < 35 mm Hg), during Sev alone, and Sev plus hypoxia. In awake rabbits hypoxia produced an increase in VE and VT (p<0.05) while f was unchanged. HR fell and AP rose (p<0.05). During normoxia, VT increased and f decreased with all concentrations of Sev, while VE only fell at 0.37% and 1.86% (p<0.05). HR increased with at all concentrations while AP decreased at 0.37% and 1.86% (p<0.05). With hypoxia and Sev, the increase in VT was the same as awake levels at all concentrations associated with a small rise in f (p<0.05). VE increased to levels seen in the awake state at lower concentrations of Sev but was attenuated at 1.86% (p<0.05). The hypoxia induced bradycardia and rise in AP were attenuated by increasing doses of Sev and abolished at 1.86% (p<0.05). Sub‐anesthetic depressant effects of Sev on the cardiorespiratory responses to hypoxia are selective and therefore unlikely to be the result of carotid body inhibition.Grant Funding Source: Supported by John Hunter Hospital Charitable Trust

WIDE AWAKE Mediates the Circadian Timing of Sleep Onset

How the circadian clock regulates the timing of sleep is poorly understood. Here, we identify a Drosophila mutant, wide awake (wake), that exhibits a marked delay in sleep onset at dusk. Loss of WAKE in a set of arousal-promoting clock neurons, the large ventrolateral neurons (l-LNvs), impairs sleep onset. WAKE levels cycle, peaking near dusk, and the expression of WAKE in l-LNvs is Clock dependent. Strikingly, Clock and cycle mutants also exhibit a profound delay in sleep onset, which can be rescued by restoring WAKE expression in LNvs. WAKE interacts with the GABAA receptor Resistant to Dieldrin (RDL), upregulating its levels and promoting its localization to the plasma membrane. In wake mutant l-LNvs, GABA sensitivity is decreased and excitability is increased at dusk. We propose that WAKE acts as a clock output molecule specifically for sleep, inhibiting LNvs at dusk to promote the transition from wake to sleep.

Treating hypertension by targeting orexin receptors: potential effects on the sleep-related blood pressure dipping profile

Treating hypertension by targeting orexin receptors: potential effects on the sleep-related blood pressure dipping profile

Chronic stress exposure decreases the cortisol awakening response in healthy young men

Academic examination is a major stressor for students in China. Investigation of stress-sensitive endocrine responses to major examination stress serves as a good model of naturalistic chronic psychological stress in an otherwise healthy population. The cortisol awakening response (CAR) is an endocrine marker of the hypothalamic-pituitary-adrenocortical (HPA) axis in response to stress. However, it remains unknown how chronic examination stress impacts the CAR in a young healthy population To exclude the influence of sex effects on hormone level, the CAR and psychological stress responses were assessed on two consecutive workdays in 42 male participants during their preparations for the Chinese National Postgraduate Entrance Exam (NPEE) and 21 non-exam, age-matched male comparisons. On each day, four saliva samples were collected immediately after awakening, 15 minutes, 30 minutes and 60 minutes after awakening. The waking level (S1), the increase within 30 minutes after awakening (R30), the area under the curve with respect to ground (AUCg), and the area under the curve with respect to increase (AUCi) were used to quantify the CAR. Psychological stress and anxiety were assessed by the Perceived Stress Scale and the Spielberger State-Trait Anxiety Inventory, respectively. Male participants in the exam group had greater perceived stress and anxiety scores relatibe to the non-exam group. Both R30 and AUCi in the exam group were significantly lower than the comparison group and this effect was most pronounced for participants with high levels of perceived stress in the exam group. Perceived stress and anxiety levels were negatively correlated with both R30 and AUCi. Chronic examination stress can lead to the decrease of CAR in healthy young men, possibly due to reduced HPA axis activity under long-term sustained stress.

Underestimation of cardiac vagal control in regular exercisers by 24-hour heart rate variability recordings

Objective To examine whether ceiling effects at long inter beat intervals (IBIs)cause an underestimation of cardiac vagal control in regular exercisers by time and frequency-domain measures of respiratory sinus arrhythmia (RSA). Methods 24-hour ECG and respiration recordings were performed in 26 regularly exercising subjects, actively engaged in aerobic training for the past year, and enrolled in supervised training in the six weeks pre-study, and in 26 age- and sex-matched non-exercisers. Sleep and waking levels of cardiac vagal control were estimated by RSA obtained through the peak–valley method, by the standard deviation of the IBIs, the root mean square of successive IBIs, and the high frequency IBI spectral power. Results In 11 of the exercisers the IBI–RSA relationship was characterized by a quadratic relationship. This reflected a ceiling effect at very long IBI values attained by regular exercisers, particularly during the nighttime recording. Irrespective of this ceiling effect, RSA as well as other heart rate variability (HRV) measures was still significantly larger in the exercisers with a quadratic IBI–RSA relationship than in non-exercisers or exercisers with a linear IBI–RSA relationship. Conclusions We conclude that a subgroup of regular exercisers is characterized by a low heart rate paired to high levels of cardiac vagal control. In these exercisers, vagal control is underestimated from HRV measures in ambulatory recordings. Inspection of the IBI–RSA relationship should be routinely added when HRV measures are used to index cardiac vagal control.

Negative emotionality, depressive symptoms and cortisol diurnal rhythms: Analysis of a community sample of middle-aged males

Prior research suggests that individuals with particular personality traits, like negative emotionality, are at greater risk for adverse health outcomes. Despite bivariate associations between negative emotionality, depressive symptoms and the hypothalamic pituitary adrenal axis (HPA axis), few studies have sought to understand the biological pathways through which negative emotionality, depressive symptomatology and cortisol—one of the primary hormonal products of the HPA axis—are associated. The present study explored whether negative emotionality influenced cortisol dysregulation through current depressive symptomatology and whether negative emotionality served as a moderator of the relationship between depressive symptoms and cortisol. In the community-based Vietnam Era Twin Study of Aging, 783 male twins completed two days of cortisol saliva sampling in their natural environments. Three measures of cortisol were analyzed: waking levels, the cortisol awakening response, and the peak to bed slope. Depressive symptoms significantly mediated the associations between negative emotionality and the peak to bed slope. A 2-way interaction between depressive symptoms and negative emotionality was significant for the peak to bed slope and for waking levels of cortisol. Exploration of the interactions illustrated that depressive symptoms only affected cortisol slopes at average or high levels of negative emotionality and only affected waking levels at low levels of negative emotionality. Negative emotionality and depressive symptoms were not related to the cortisol awakening response. This is the first study to find indirect associations between negative emotionality and peak to bed cortisol slopes through depressive symptoms. These findings illustrate the complex interplay between personality characteristics, depressive symptoms and different indices of the cortisol diurnal rhythm.

Endogenous GABA Levels in the Pontine Reticular Formation Are Greater during Wakefulness than during Rapid Eye Movement Sleep

Studies using drugs that increase or decrease GABAergic transmission suggest that GABA in the pontine reticular formation (PRF) promotes wakefulness and inhibits rapid eye movement (REM) sleep. Cholinergic transmission in the PRF promotes REM sleep, and levels of endogenous acetylcholine (ACh) in the PRF are significantly greater during REM sleep than during wakefulness or non-REM (NREM) sleep. No previous studies have determined whether levels of endogenous GABA in the PRF vary as a function of sleep and wakefulness. This study tested the hypothesis that GABA levels in cat PRF are greatest during wakefulness and lowest during REM sleep. Extracellular GABA levels were measured during wakefulness, NREM sleep, REM sleep, and the REM sleep-like state (REM(Neo)) caused by microinjecting neostigmine into the PRF. GABA levels varied significantly as a function of sleep and wakefulness, and decreased significantly below waking levels during REM sleep (-42%) and REM(Neo) (-63%). The decrease in GABA levels during NREM sleep (22% below waking levels) was not statistically significant. Compared with NREM sleep, GABA levels decreased significantly during REM sleep (-27%) and REM(Neo) (-52%). Comparisons of REM sleep and REM(Neo) revealed no differences in GABA levels or cortical EEG power. GABA levels did not vary significantly as a function of dialysis site within the PRF. The inverse relationship between changes in PRF levels of GABA and ACh during REM sleep indicates that low GABAergic tone combined with high cholinergic tone in the PRF contributes to the generation of REM sleep.

Cerebral oxygenation in wake and during sleep and its relationship to cognitive function in community-dwelling older adults without sleep disordered breathing.

This descriptive cross-sectional study investigated the relationships between cerebral oxygen reserve and cognitive function in community-dwelling older adults. Participants (72 women and 40 men) underwent standard polysomnography, including regional measures of percent oxyhemoglobin saturation (rcSO(2)) determined by cerebral oximetry. Two variables were used to calculate cerebral oxygen reserve: (a) awake rcSO(2) (mean presleep rcSO(2)) and (b) the change in rcSO(2) from before sleep to the end of the first non-rapid-eye movement cycle. General linear models, adjusted for the effects of education and occupation, tested differences in performance on standard tests of memory, attention, and speed of mental processing. Awake rcSO(2) values were normal (60%-79.9%) in 64 participants, marginal (50%-59.9%) in 41, and low (43%-49.9%) in 7. Participants with normal awake levels had higher cognitive function than those with low levels (p < .05). Changes in rcSO(2) were greatest in participants with marginal awake rcSO(2) values; among whom, those who increased rcSO(2) during sleep (n = 17) had better memory function than the 24 who did not (p < .05). Low awake rcSO(2) values mark individuals with low cerebral oxygen reserves and generally lower cognitive function; marginal awake rcSO(2) values that fall during sleep may indicate loss of cerebral oxygen reserve and an increased risk for cognitive decline. Further studies may clarify the significance of and mechanisms underlying individual differences in awake rcSO(2) and the changes that occur in rcSO(2) while asleep.

Predicting Nocturnal Hypoventilation in Hypercapnic Chronic Obstructive Pulmonary Disease Patients Undergoing Long-Term Oxygen Therapy

Background: Chronic obstructive pulmonary disease (COPD) patients are very sensitive to changes in pulmonary mechanics and central ventilation control during sleep and may develop significant gas exchange alterations with increased hypoxemia and hypercapnia. Oxygen therapy improves nocturnal desaturation but can worsen hypoventilation. Objectives: To analyze the prevalence of nocturnal hypoventilation (NHV) in hypercapnic COPD patients and to determine predictive factors for this phenomenon. Methods: This was a prospective multicenter study which enrolled 80 clinically stable COPD patients with hypercapnic respiratory failure who fulfilled the conventional criteria for long-term oxygen therapy (LTOT). All patients had undergone pulmonary function testing, blood gas analysis, and respiratory polygraphy. Arterial blood gas samples were obtained while patients were awake and during sleep. NHV was considered when an increase in PaCO₂ >10 mm Hg was observed in any nocturnal arterial blood gas sample as compared to the awake levels. Results: Seventeen patients (21%) developed NHV. NHV was associated with the values of BMI, hemoglobin, hematocrits, DLCO, and PaO₂ reached after oxygen administration. In the logistic regression analysis BMI (OR 1.26, 95% CI 1.068–1.481; p = 0.006) and the diurnal increase of PaO₂ after O₂ (OR 0.89, 95% CI 0.807–0.972; p = 0.010) were the variables that best discriminated with a sensitivity of 82% and a specificity of 78%. Conclusions: NHV is a relatively common finding in stable hypercapnic COPD patients undergoing LTOT and it is related to a higher BMI and lower PaO₂ after oxygen administration.

Education and Levels of Salivary Cortisol Over the Day in US Adults

Dysregulation of the hypothalamic-pituitary-adrenal axis is hypothesized to be an important pathway linking socioeconomic position and chronic disease. This paper tests the association between education and the diurnal rhythm of salivary cortisol. Up to eight measures of cortisol (mean of 5.38 per respondent) over 2 days were obtained from 311 respondents, aged 18-70, drawn from the 2001-2002 Chicago Community Adult Health Study. Multi-level models with linear splines were used to estimate waking level, rates of cortisol decline, and area-under-the-curve over the day, by categories of education. Lower education (0-11 years) was associated with lower waking levels of cortisol, but not the rate of decline of cortisol, resulting in a higher area-under-the-curve for more educated respondents throughout the day. This study found evidence of lower cortisol exposure among individuals with less education and thus does not support the hypothesis that less education is associated with chronic over-exposure to cortisol.

Event-related potentials as a measure of sleep disturbance: A tutorial review

This article reviews event-related potentials (ERPs) the minute responses of the human brain that are elicited by external auditory stimuli and how the ERPs can be used to measure sleep disturbance. ERPs consist of a series of negative- and positive-going components. A negative component peaking at about 100 ms, N1, is thought to reflect the outcome of a transient detector system, activated by change in the transient energy in an acoustic stimulus. Its output and thus the amplitude of N1 increases as the intensity level of the stimulus is increased and when the rate of presentation is slowed. When the output reaches a certain critical level, operations of the central executive are interrupted and attention is switched to the auditory channel. This switching of attention is thought to be indexed by a later positivity, P3a, peaking between 250 and 300 ms. In order to sleep, consciousness for all but the most relevant of stimuli must be prevented. Thus, during sleep onset and definitive non-rapid eye movement (NREM) sleep, the amplitude of N1 diminishes to near-baseline level. The amplitude of P2, peaking from 180 to 200 ms, is however larger in NREM sleep than in wakefulness. P2 is thought to reflect an inhibitory process protecting sleep from irrelevant disturbance. As stimulus input becomes increasingly obtrusive, the amplitude of P2 also increases. With increasing obtrusiveness particularly when stimuli are presented slowly, a later large negativity, peaking at about 350 ms, N350, becomes apparent. N350 is unique to sleep, its amplitude also increasing as the stimulus becomes more obtrusive. Many authors postulate that when the N350 reaches a critical amplitude, a very large amplitude N550, a component of the K-Complex is elicited. The K-Complex can only be elicited during NREM sleep. The P2, N350 and N550 processes are thus conceived as sleep protective mechanisms, activated sequentially as the risk for disturbance increases. During REM sleep, the transient detector system again becomes somewhat activated, the amplitude of N1 reaching from 15 to 40% of its waking level. Very intense and/or very infrequently presented stimuli might elicit a P3-like deflection suggesting an intrusion into some aspect of consciousness. The types of experimental paradigms used in most ERP studies are quite different from those used in the study of noise and its effects on sleep. ERP studies will need to employ procedures that have greater ecological generalization; stimulus intensity needs to be lower, less abrupt, with much longer durations, and importantly, stimuli should be presented much less often.

Hypocretin-2 Saporin Lesions of the Ventrolateral Periaquaductal Gray (vlPAG) Increase REM Sleep in Hypocretin Knockout Mice

Ten years ago the sleep disorder narcolepsy was linked to the neuropeptide hypocretin (HCRT), also known as orexin. This disorder is characterized by excessive day time sleepiness, inappropriate triggering of rapid-eye movement (REM) sleep and cataplexy, which is a sudden loss of muscle tone during waking. It is still not known how HCRT regulates REM sleep or muscle tone since HCRT neurons are localized only in the lateral hypothalamus while REM sleep and muscle atonia are generated from the brainstem. To identify a potential neuronal circuit, the neurotoxin hypocretin-2-saporin (HCRT2-SAP) was used to lesion neurons in the ventral lateral periaquaductal gray (vlPAG). The first experiment utilized hypocretin knock-out (HCRT-ko) mice with the expectation that deletion of both HCRT and its target neurons would exacerbate narcoleptic symptoms. Indeed, HCRT-ko mice (n = 8) given the neurotoxin HCRT2-SAP (16.5 ng/23nl/sec each side) in the vlPAG had levels of REM sleep and sleep fragmentation that were considerably higher compared to HCRT-ko given saline (+39%; n = 7) or wildtype mice (+177%; n = 9). However, cataplexy attacks did not increase, nor were levels of wake or non-REM sleep changed. Experiment 2 determined the effects in mice where HCRT was present but the downstream target neurons in the vlPAG were deleted by the neurotoxin. This experiment utilized an FVB-transgenic strain of mice where eGFP identifies GABA neurons. We verified this and also determined that eGFP neurons were immunopositive for the HCRT-2 receptor. vlPAG lesions in these mice increased REM sleep (+79% versus saline controls) and it was significantly correlated (r = 0.89) with loss of eGFP neurons. These results identify the vlPAG as one site that loses its inhibitory control over REM sleep, but does not cause cataplexy, as a result of hypocretin deficiency.

Using Magnetic Resonance Spectroscopy in Narcolepsy to Study the Limbic Mechanisms of Cataplexy

Using Magnetic Resonance Spectroscopy in Narcolepsy to Study the Limbic Mechanisms of Cataplexy

공연 시 배우의 각성변화와 심리적 자기조절 분석

본 연구는 공연 시 배우의 심박수의 각성변화와 유발된 각성상태에 대한 심리적 자기조절을 분석하는데 그 목적이 있다. 연구대상자는 연극 전문극단에 소속되어 있는 배우 5명을 목적적 표본추출하였다. 각성변화를 측정하기 위해서 심박수 측정기를 활용하였고, 자기조절 행동을 관찰 및 기록할 수 있는 행동 관찰지를 사용하였으며, 공연종료 후 개인별 심층상담을 실시하였다. 심박수 변화에 대한 평균과 표준편차를 산출하여, 공연 시간대별 변화 추이를 그래프화 하였으며, 자기조절 행동을 분석하기 위해 질적 연구방법을 실시하였다. 도출된 연구결과는 다음과 같다. 첫째, 배우들은 공연이 시작되기 전부터 심박수의 각성수준이 높아지는 변화를 나타냈으며, 공연 시작 20분 전부터 5분 전까지 가장 높은 각성상태를 보였다. 둘째, 공연 시작 전 심호흡, 호흡 가다듬기, 자기대화, 배우들과의 대화, 대본연습에 집중, 화장실 가기, 흡연, 복장점검 등의 자기조절적 행동을 나타냈다. 셋째, 공연 시 높아진 각성상태를 조절하기 위해서 이완기법, 자기집중화, 자신감강화, 상황대처 및 적응 등과 같은 심리적 자기조절 방법을 사용하는 것으로 나타났다. The purpose of this study was to analyze self-regulation about changing heart rate and perceived arousal variation when actors start their performance. Object of this study were 5 actors who belong to the theater selected using the purposive sampling method. This study used a measuring instrument of heart rate to measure arousal status, used behavior observation paper to observe and record self-regulation behavior and executed personal consultation after ending performance. There was graph mad by variation transition which calculated average and standard deviation about variation of heart rate each time of performance. The results of this study were as follows. First, there were high variation of awake level that actor's heart rates were rising before starting performance and the most high level of arousal was from 20minutes to 5minutes before starting performance. Second, there were self-regulation behaviors appeared such as deep breathing, breath controling, self talking, talking with other actors, concentrating an script, going to toilet, smoking, checking closes before starting performance. Third, when performance start, actors used psychological self-regulational method such as relaxation, self concentration, confidence reinforcement, coping with state or accommodation for controling raised arousal status.

Subjective evaluation of community noise in Canada's National Capital Region and its relation to waking levels of salivary biomarkers.

Some research has suggested an association between long‐term exposure to traffic noise and relative risk of cardiovascular disease (Babisch et al., 2005; Willich et al., 2006). It has been assumed that noise may act as a nonspecific stressor. Acute exposure to noise can evoke physiological and behavioral changes reminiscent of a stress response in rodents (Michaud et al., 2003), but it is equivocal that this occurs in humans chronically exposed to traffic noise. This pilot project examined annoyance to community noise and salivary biomarkers known to be influenced by stressor exposure. A face‐to‐face interview subjectively assessed community noise for 60 residents (30 males, 30 females; mean age 41.3, SD=14.98). Traffic sound levels will be determined and respondents categorized into high (>65 dBA, Leq24) and low (<50 dBA) noise areas. Participants also provided saliva samples upon awakening, 30 min after awakening, and prior to bedtime. Concentrations of salivary biomarkers of alpha‐amylase and cortisol were spectrophotometrically determined using commercial enzyme‐linked immunosorbant assays. Two‐way (high‐noise versus low‐noise) mixed‐model analyses of variance will examine differences in questionnaire and salivary responses. Sex differences will be evaluated with independent t‐tests, and polynomial regression analyses will relate salivary biomarker levels to high‐ or low‐noise areas.

Subclinical Anxiety Symptoms, Sleep, and Daytime Dysfunction in Older Adults With Primary Insomnia

Both insomnia complaints and anxiety disorders are common in older adults, and are associated with poor daytime functioning. The present study investigated whether subclinical levels of anxiety were associated with sleep disturbance and daytime functioning in older adults who met diagnostic criteria for primary insomnia, and therefore did not meet criteria for depression or an anxiety disorder. After adjustment for depressive symptoms, elevated state anxiety was associated with higher levels of wake after sleep onset (measured by both actigraphy and sleep log) and shorter sleep onset latency (measured by sleep log). Higher levels of trait anxiety were associated with greater wake after sleep onset (measured by sleep log). Elevated state and trait anxiety were associated with worse social functioning, and higher levels of trait anxiety were associated with worse role functioning. Thus, subclinical anxiety symptoms may be an important target for clinical intervention to improve sleep and functioning in older adults with primary insomnia.

Subjective evaluation of community noise in Canada's National Capital Region and its relation to waking levels of salivary biomarkers

Some research has suggested an association between long‐term exposure to traffic noise and relative risk of cardiovascular disease (Babisch et al., 2005; Willich et al., 2006). It has been assumed that noise may act as a nonspecific stressor. Acute exposure to noise can evoke physiological and behavioural changes reminiscent of a stress response in rodents (Michaud et al., 2003), but it is equivocal that this occurs in humans chronically exposed to traffic noise. This pilot project examined annoyance to community noise and salivary biomarkers known to be influenced by stressor exposure. A face‐to‐face interview subjectively assessed community noise for 60 residents (30 males, 30 females; mean age 41.3, SD = 14.98). Traffic sound levels will be determined and respondents categorized into high (>65 dBA, Leq24) and low (<50 dBA) noise areas. Participants also provided saliva samples upon awakening, 30‐min after awakening, and prior to bedtime. Concentrations of salivary biomarkers of alpha‐amylase and cortis...

Retraction: Subclinical Anxiety Symptoms, Sleep, and Daytime Dysfunction in Older Adults With Primary Insomnia

"Both Insomnia complaints and anxiety-related distress are common in older adults, and are associated with poor daytime functioning. We investigated whether subclinical levels of anxiety were associated with sleep disturbance and daytime functioning in older adults who met diagnostic criteria for primary insomnia, and therefore but did not meet criteria for depression or an anxiety disorder. After adjustment for depressive symptoms, elevated state anxiety was associated with higher levels of wake after sleep onset (measured by both actigraphy and sleep log) and shorter sleep sleep onset latency (measured by sleep log). Higher levels of trait anxiety were associated with greater wake after sleep onset (measured by sleep log). Elevated state and trait anxiety were associated with worse and social functioning, and higher levels of trait anxiety were associated with worse role functioning. Thus, subclinical anxiety symptoms may be an important target for clinical intervention to improve sleep and functioning in older adults with primary insomnia."

Effects of Saporin-Induced Lesions of Three Arousal Populations on Daily Levels of Sleep and Wake

The hypocretin (HCRT) neurons are located only in the perifornical area of the lateral hypothalamus and heavily innervate the cholinergic neurons in the basal forebrain (BF), histamine neurons in the tuberomammillary nucleus (TMN), and the noradrenergic locus ceruleus (LC) neurons, three neuronal populations that have traditionally been implicated in regulating arousal. Based on the innervation, HCRT neurons may regulate arousal by driving these downstream arousal neurons. Here, we directly test this hypothesis by a simultaneous triple lesion of these neurons using three saporin-conjugated neurotoxins. Three weeks after lesion, the daily levels of wake were not changed in rats with double or triple lesions, although rats with triple lesions were asleep more during the light-to-dark transition period. The double- and triple-lesioned rats also had more stable sleep architecture compared with nonlesioned saline rats. These results suggest that the cholinergic BF, TMN, and LC neurons jointly modulate arousal at a specific circadian time, but they are not essential links in the circuitry responsible for daily levels of wake, as traditionally hypothesized.

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.