Chronobiology International Vol. 9, No. 6, pp. 444-441 0 I992 International Society of Chronobiology
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Circadian Rhythm in Plasma Noradrenaline of Healthy Sleep-Deprived Subjects Mirande Candito, *Dominique Pringuey, tYves Jacomet, *Eric Souetre, *Edouard Salvati, $Jean-Louis Ardisson, Pierre Chambon, and *Guy Darcourt Laboratoire de Biochimie, and W i n i q u e de Psychiatrie et de Psychologie Mkdicale, H6pital Pasteur: and Laboratoires de j-Pharmacologie et de SPhysiologie, Facultk de Mkdecine, Chemin de Valombrose, Nice, France
Summary: Under normal sleep-wake conditions, noradrenaline (NA) secretions in supine subjects exhibit a weak circadian variation with a peak that occurs around noon; the sleep span is characterized by reduced NA secretion. Some investigators have reported that the circadian NA rhythm is completely obliterated during sleep deprivation. In our laboratory, plasma NA was assayed every hour for 24 h in nine healthy men 20-23 years of age. All men were deprived of sleep and were required to eat and walk around every hour to prevent sleep. However, subjects remained supine for 20 min before blood samples were collected to eliminate the effect of activity. Persistence of a slight decrease in the night concentration in several subjects, despite sleep deprivation, suggests that NA secretion may be influenced by a biological clock whose activity becomes visible when the influence of posture is removed. Key Words: Plasma noradrenalineCircadian rhythm-Sleep deprivation.
The diurnal rhythm of plasma noradrenaline (NA) secretion has been studied extensively (1-5). Concentrations peak early in the afternoon and decrease to their lowest level at night. Daily fluctuations could arise directly from an endogenous biological clock that regulates NA neuronal activity. However, NA concentrations fluctuate as a function of the subject’s posture, which appears to have a greater effect on NA levels than the circadian rhythm (3). NA levels are also affected by other external factors, acting as masking effects ( 6 ) ,including physical exercise, exposure to cold (7), and stress (8). Although some investigators report conservation of a circadian rhythm of urinary NA (9), others have described relative constancy of urinary catecholamine excretion over 24 h subsequent to sleep deprivation (10).Sleep deprivation also has been suggested to abolish the plasma NA rhythm ( 1 1,12), and when Received May 1991; accepted with revisions December 27, 1991. Address correspondence and reprint requests to Dr. M. Candito, Laboratoire de Biochimie, HBpital Pasteur, BP 69,06002 Nice Cedex, France.
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CIRCADIAN RHYTHM AND SLEEP DEPRIVATION
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sleep is delayed, the decrease in NA secretions is delayed in a parallel manner. The NA level has thus been considered a direct response to modifications in posture (2), and the circadian NA rhythm could reflect adaptation to changes in posture ( 13). In view of these contradictory findings, and because previous research has not clearly established whether the circadian NA rhythm is related to sleep or simply to posture, the present study was conducted to investigate whether the diurnal NA rhythm persists when subjects are sleep deprived. Diurnal sympathetic neuronal activity is maintained at night, a situation that offers two advantages: if a diurnal NA rhythm persists, it is not due to lowering of the sympathetic tonus linked to posture, and activity prevents subjects from sleeping. Plasma NA was assayed by a highly sensitive method in hourly blood samples obtained over 24 h from nine healthy young men deprived of sleep. Subjects were required to eat lightly and walk about every hour to avoid sleep; this protocol reproduced the same study conditions each hour, particularly the same neuronal activity. Subjects were supine for 20 min before blood sampling to eliminate the masking effect of upright posture on the basal NA level (7).
SUBJECTS AND METHODS Nine men 20-23 years of age with no personal history of psychiatric illness or endocrine or metabolic disease were studied in a single sleep deprivation protocol over 24 h. Before the study, they were synchronized with a diurnal activity from 07:OO to 23:OO h and a nocturnal rest. The study was performed during February. Every hour, all subjects were given a light, calorie-equivalent snack (excluding coffee, tea, chocolate, banana, lemon, or orange). Twenty minutes before the first sample, an indwelling venous catheter was inserted; patency was maintained throughout the entire experiment by a slow infusion of 5% glucose. Subjects were supine during the 20 min before each blood sample, but were requested to talk softly to keep awake; after blood samples were taken, subjects were required to get up and walk around. A4 ascorbic Blood samples were collected into tubes containing heparin and acid, and were immediately placed on ice for rapid centrifugation at -4°C. The plasma was then frozen at -20°C and analyzed in
Chronobiol Int Downloaded from informahealthcare.com by University of Auckland on 10/27/14 For personal use only.
Circadian Rhythm in Plasma Noradrenaline of Healthy Sleep-Deprived Subjects Mirande Candito, *Dominique Pringuey, tYves Jacomet, *Eric Souetre, *Edouard Salvati, $Jean-Louis Ardisson, Pierre Chambon, and *Guy Darcourt Laboratoire de Biochimie, and W i n i q u e de Psychiatrie et de Psychologie Mkdicale, H6pital Pasteur: and Laboratoires de j-Pharmacologie et de SPhysiologie, Facultk de Mkdecine, Chemin de Valombrose, Nice, France
Summary: Under normal sleep-wake conditions, noradrenaline (NA) secretions in supine subjects exhibit a weak circadian variation with a peak that occurs around noon; the sleep span is characterized by reduced NA secretion. Some investigators have reported that the circadian NA rhythm is completely obliterated during sleep deprivation. In our laboratory, plasma NA was assayed every hour for 24 h in nine healthy men 20-23 years of age. All men were deprived of sleep and were required to eat and walk around every hour to prevent sleep. However, subjects remained supine for 20 min before blood samples were collected to eliminate the effect of activity. Persistence of a slight decrease in the night concentration in several subjects, despite sleep deprivation, suggests that NA secretion may be influenced by a biological clock whose activity becomes visible when the influence of posture is removed. Key Words: Plasma noradrenalineCircadian rhythm-Sleep deprivation.
The diurnal rhythm of plasma noradrenaline (NA) secretion has been studied extensively (1-5). Concentrations peak early in the afternoon and decrease to their lowest level at night. Daily fluctuations could arise directly from an endogenous biological clock that regulates NA neuronal activity. However, NA concentrations fluctuate as a function of the subject’s posture, which appears to have a greater effect on NA levels than the circadian rhythm (3). NA levels are also affected by other external factors, acting as masking effects ( 6 ) ,including physical exercise, exposure to cold (7), and stress (8). Although some investigators report conservation of a circadian rhythm of urinary NA (9), others have described relative constancy of urinary catecholamine excretion over 24 h subsequent to sleep deprivation (10).Sleep deprivation also has been suggested to abolish the plasma NA rhythm ( 1 1,12), and when Received May 1991; accepted with revisions December 27, 1991. Address correspondence and reprint requests to Dr. M. Candito, Laboratoire de Biochimie, HBpital Pasteur, BP 69,06002 Nice Cedex, France.
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Chronobiol Int Downloaded from informahealthcare.com by University of Auckland on 10/27/14 For personal use only.
CIRCADIAN RHYTHM AND SLEEP DEPRIVATION
445
sleep is delayed, the decrease in NA secretions is delayed in a parallel manner. The NA level has thus been considered a direct response to modifications in posture (2), and the circadian NA rhythm could reflect adaptation to changes in posture ( 13). In view of these contradictory findings, and because previous research has not clearly established whether the circadian NA rhythm is related to sleep or simply to posture, the present study was conducted to investigate whether the diurnal NA rhythm persists when subjects are sleep deprived. Diurnal sympathetic neuronal activity is maintained at night, a situation that offers two advantages: if a diurnal NA rhythm persists, it is not due to lowering of the sympathetic tonus linked to posture, and activity prevents subjects from sleeping. Plasma NA was assayed by a highly sensitive method in hourly blood samples obtained over 24 h from nine healthy young men deprived of sleep. Subjects were required to eat lightly and walk about every hour to avoid sleep; this protocol reproduced the same study conditions each hour, particularly the same neuronal activity. Subjects were supine for 20 min before blood sampling to eliminate the masking effect of upright posture on the basal NA level (7).
SUBJECTS AND METHODS Nine men 20-23 years of age with no personal history of psychiatric illness or endocrine or metabolic disease were studied in a single sleep deprivation protocol over 24 h. Before the study, they were synchronized with a diurnal activity from 07:OO to 23:OO h and a nocturnal rest. The study was performed during February. Every hour, all subjects were given a light, calorie-equivalent snack (excluding coffee, tea, chocolate, banana, lemon, or orange). Twenty minutes before the first sample, an indwelling venous catheter was inserted; patency was maintained throughout the entire experiment by a slow infusion of 5% glucose. Subjects were supine during the 20 min before each blood sample, but were requested to talk softly to keep awake; after blood samples were taken, subjects were required to get up and walk around. A4 ascorbic Blood samples were collected into tubes containing heparin and acid, and were immediately placed on ice for rapid centrifugation at -4°C. The plasma was then frozen at -20°C and analyzed in
