Disturbances in hormonal profiles of night workers during their usual sleep and work times.

In a previous study, the authors reported that the 24-h rhythms of pituitary and adrenal hormones--that is, thyrotropin (TSH), prolactin (PRL), growth hormone, and cortisol--adapted only partially in a group of permanent night workers. However, the real impact of circadian rhythm alterations on the health and well-being of subjects is still unclear. In this study, the authors focus on an ergonomic field and address questions of adaptation of these hormones during the usual day sleep time (0700-1500 h) and during the usual night work time (2200-0600 h) in permanent night workers. Eleven night workers, working a night schedule for at least 2 years, submitted to a high-frequency blood sampling procedure (10 min) and to electroencephalographic recordings during sleep. The endocrine profiles of night workers were compared to those of day-active subjects studied during their usual sleep-wake schedule. During usual day sleep, despite an adapted sleep structure, cortisol levels among night workers were abnormally enhanced, whereas the TSH decreased in comparison to the plateau observed among day-active subjects. During usual work time, some hormonal disturbances persisted, in particular concerning cortisol and PRL (two hormones known to reflect the level of activation). Among night workers, the work time was associated with the quiescent period of cortisol secretion normally occurring during the first hours of sleep, and with a transient PRL increase. These results revealed altered hormonal profiles during the sleep time of night workers that do not result in an altered sleep pattern. The nocturnal work time, which requires a high level physical and mental performance, is associated with some endocrine alterations reflecting an eventual phase of hypovigilance.

Disruption of endocrine rhythms in sleeping sickness with preserved relationship between hormonal pulsatility and the REM-NREM sleep cycles.

In human African trypanosomiasis (sleeping sickness), sleep and wake episodes are sporadically distributed throughout the day and the night. To determine whether these sleep disturbances affect the 24-h hormone profiles and the normal relationships between hormone pulsatility and sleep stages, polygraphic sleep recordings and concomitant hormone profiles were obtained in 6 African patients with sleeping sickness and in 5 healthy African subjects selected from Abidjan on the Ivory Coast. Polysomnographic recordings were continuous, and blood was taken every 10 min throughout the 24-h period. Plasma was analyzed for cortisol, prolactin, and plasma renin activity (PRA). The 24-h rhythm of cortisol, considered to be an endogenous circadian rhythm, was attenuated in all of the patients except one. However, as in normal subjects, slow wave sleep (SWS) remained associated with the declining phases of the cortisol secretory episodes. Prolactin and PRA profiles, which are strongly influenced by the sleep-wake cycle, did not manifest the nocturnal increase normally associated with the sleep period; instead, they reflected a sporadic distribution of the sleep and wake episodes throughout the 24-h period. In patients with sleeping sickness as in normal subjects, rapid eye movement (REM) sleep began during the descending phases of prolactin pulses. In both groups, PRA reflected the sleep stage distribution with non REM (NREM) sleep occurring during the ascending phases and REM sleep during the descending phases of the PRA oscillations. However, in sleeping sickness patients, the marked sleep fragmentation often did not allow sufficient time for PRA to increase significantly, as is normally the case in subjects with regular NREM-REM sleep cycles. These results demonstrate that, together with the disruption of the sleep-wake cycle, there are profound differences in the temporal organization of the 24-h hormone profiles in humans with African trypanosomiasis. However, the relationship between hormonal pulses and specific sleep stages persists, indicating the existence of a robust link between hormonal release and the internal sleep structure.

Circulating adrenomedullin is increased after heart transplantation.

OBJECTIVE: Adrenomedullin (ADM), secreted by the failing human heart, is a newly discovered potent endogenous vasorelaxing and natriuretic peptide that may play a role in cardiorenal regulation. No data are available on ADM in heart-transplant recipients (Htx) and the aim of this study was to determine the short- and long-term responses of ADM after heart transplantation. METHODS: Circulating ADM and its relationship with parameters of cardiovascular hemodynamics, humoral factors and renal function were determined in normal subjects and Htx early (1, 2, 4, 8, 15 and 30 days) and late (32 +/- 16 months) after transplantation. Additionally, ADM was obtained in matched hypertensive and renal-transplant patients (n = 9 in each group). RESULTS: Plasma ADM, elevated in heart failure patients, further increased transiently at day 1 after transplantation (from 37.9 +/- 15.9 to 125.8 +/- 15.3 pmol/l, P < 0.01) and, although decreasing thereafter, remained elevated until the 30th day after transplantation (52.1 +/- 25.2 pmol/l). Late after transplantation. ADM concentrations were still increased compared to normal values (31.3 +/- 5.3 vs. 19.4 +/- 2.7 pmol/l, P < 0.001). ADM positively correlated with endothelin, atrial natriuretic peptide (ANP) and cyclosporine. ADM was also correlated with increased diastolic (r = 0.68, P < 0.04) and systolic (r = 0.66, P < 0.05) blood pressure in late Htx. No relationship was observed between ADM and left ventricular mass index, aldosterone and creatinine. ADM elevation was similar in hypertensive, renal-transplant patients and in Htx. CONCLUSIONS: Circulating ADM is increased after heart transplantation, in relation to hypertension, endothelin, cyclosporine and ANP. In view of ADM's biological properties, these results might suggest a compensatory role for ADM against further development of vasoconstriction and fluid retention states after heart transplantation.

Plasma free cortisol during secretory episodes.

Plasma free cortisol fractions were determined in normal men during spontaneous cortisol secretory episodes and ACTH- or exercise-provoked cortisol peaks in the physiological range. The percentage of free cortisol was measured using ultrafiltration by centrifugation at 37 C, and total cortisol concentrations were measured by RIA. The percent free cortisol varied with the time of day, as did total cortisol. It increased parallel to total cortisol increases, whether they were spontaneous, as occurring in the early morning or postprandially, or provoked by external stimulation. A highly significant positive correlation between relative increases in free and total cortisol was found throughout the experiment. As reported previously, total cortisol increases, according to their origin, did or did not reduce the effects of subsequent stimuli. The present results indicate that the variations in the percent free cortisol are not responsible for the differences in the cortisol responses to these stimuli.

Influence of timing and intensity of musclar exercise on temporal patterns of plasma cortisol levels.

Plasma concentrations of cortisol were measured in 9 subjects form 0800 h to 1800 h at 10-min intervals during resting periods and 5 min intervals during exercise and recovery. This was done to assess to effect of exercise on the patterns of plasma cortisol levels. At 1000 h, 90 min exercise at a moderate work level (55% of Vo2 max) produced a transient rise in plasma cortisol which averaged 11.9 pg/100 ml (SE plus or minus 1.2) and introduced subsequent suppression of meal-related increase, At a lower work load (25% of Vo2 max) a similar transient rise occurred, avering 11.7 pg/100 ml (SE plus or minus 2.2); latency rate of concentration change and magnitude and not significatntly different from those at a moderate work load. A strenous work level was required to produce a more rapid response with an increased secretion rate. When 90 min exercise at a moderate work levels was preformed at 1300 h. (i.e. coinciding with postprandial cortisol concentration peak), the increase in plasma cortisol concentration (1.3 pg/100ml (SE plus or minus 0.3) was significantly lower than that induced by the same exercise performed in the morning. These results demonstrate that high plasma levels of cortisol diminish the subsequent stress response and that exercise-induced and meal-induced increases are not active.

Feedback from meal-related peaks determines diurnal changes in cortisol response to exercise.

Diurnal variations in cortisol response to exercise and their relation to the events of the day were assessed by comparing daily cortisol patterns on the control day and on days when exercise was performed at different times. A remarkable midday cortisol peak coincided with the noon meal, but cortisol levels were irregularly affected by an identical meal in the evening. However, the exercise produced equal increases when performed during quiescent periods (i.e. without any secretory peaks at 1000, 1430, 1700, and 2130 h), but peak levels for exercise at 2130 h were significantly lower because of the lower basal levels in the evening. When the same exercise was performed at 1300 h (i.e. coinciding with the postprandial peak), only a brief leveling-off interrupted the decline in cortisol levels. The meal-related evening peak, if any, provoked a similar decrease in response to exercise performed at 2000 h. Similarly, the midday peak itself was reduced by a prior exercise-induced cortisol rise. These results show that the daily cortisol pattern results from the interactions between the meal-related peaks, especially the major midday cortisol peak, and the exercise-induced increases, both of which inhibit the response to subsequent stimulation. The identical responses to exercise at the different quiescent periods tested, despite a general downward trend in basal cortisol levels, establish the primacy of such feedback mechanisms over those responsible for the circadian rhythm.

Diurnal cortisol peaks and their relationships to meals.

Relationships between diurnal plasma cortisol peaks and meals were evaluated for 30 male subjects divided into 5 groups. At 1300 h, at the time of a slow increase of plasma cortisol in fasting subjects, a reproducible rapidly increasing meal-related peak appeared in all subjects studied. An identical meal at 2000 h led to a lower mean response, with larger interindividual variations. This attenuated evening response does not seem attributable to any daily rhythm in responsiveness nor to changing basal levels, since only slight nonsignificant rises in cortisol appeared after an identical meal at 1000 h. The usual mean cortisol pattern with a midday peak was observed in subjects accustomed to different activity and meal-time schedules, which excludes the role of dietary habits. Satiety did not seen to play a determining role in the response to the 1000 h meal, as was shown by comparing subjects who did or did not have breakfast after overnight fasting. Meal intake was not necessary to provoke peaking in cortisol levels, and it has been established that neural and behavioral factors associated with meal presentation play a predominant role in some subjects. The results given clear evidence of the influence of meal timing on the daily plasma cortisol pattern, but no clue was found as to why eating affects the pituitary-adrenal axis differently according to the time of day. The noon meal may at least have a synchronizing role on normally existing plasma cortisol fluctuations.

Ultradian oscillations of plasma glucose, insulin, and C-peptide in man during continuous enteral nutrition.

The profiles of plasma glucose, insulin, and C-peptide were studied in normal men receiving continuous enteral nutrition. Large oscillations occurred with periods of 53-113 min. Their mean amplitudes, expressed as a percentage of the 24-h mean, were as high as 20% for glucose, 54% for insulin, and 56% for C-peptide. The oscillations of plasma insulin levels throughout the 24 h were concomitant with those of C-peptide. Rapid 8- to 14-min plasma insulin and glucose oscillations were smaller in magnitude and could only be detected in some segments of the longer period oscillations. These results indicate that in addition to the previously described 8- to 14-min oscillations, plasma glucose, insulin, and C-peptide oscillate at a mean 80-min periodicity in man during continuous enteral nutrition. These oscillations may reflect a pancreatic oscillatory mechanism and/or cyclic variations in gastrointestinal motility or peripheral glucose uptake.

Absence of the dawn phenomenon in normal subjects.

The existence of the dawn phenomenon, defined as an increase in plasma glucose levels and/or insulin requirements in the early morning hours, is well established in diabetic patients but remains controversial in normal subjects. To verify whether this phenomenon occurs in normal subjects, the nocturnal profiles in plasma glucose, insulin, and C-peptide levels; insulin to glucose ratio; and prehepatic insulin production were studied at short intervals (4 and 10 min) in 10 normal men. The first part of the night was characterized by a decrease in all values and the presence of 1 or 2 postprandial fluctuations, followed by a steady state until 0800 h. The individual profiles were frequently superimposable, with rapid 8- to 14-min oscillations. These results do not indicate the existence of a dawn phenomenon in normal subjects.

Interactions between spontaneous and provoked cortisol secretory episodes in man.

This study describes the interactions between cortisol peaks due to spontaneous episodic release and peaks provoked by external stimuli. Successive and equidistant transitory rises of similar amplitude and duration were produced either by muscular exercise (30 min, 75% VO2max) or by injecting ACTH1-24 (Synacthen: 250 ng) before and after the midday meal-related peak. ACTH1-24 was also injected during sleep before the nocturnal sequence of the major secretory episodes. In all instances, cortisol levels had reverted to basal levels when the second stimulus was applied. ACTH-induced cortisol peaks depressed the subsequent meal-related peaks, the exercise-induced peaks, and the spontaneous secretory episodes at the end of the night, and thus had a strong depressor capacity. When exercise was the prior stimulus, the subsequent meal-related peaks were depressed, but the response to later exercise was not affected. Meal-related peaks and the spontaneous diurnal or nocturnal peaks did not depress the subsequent secretory episodes. These quantitatively comparable cortisol episodes were preceded by ACTH rises whose amplitude and duration were not identical: spontaneous and meal-related ACTH peaks were smaller than the provoked one; exercise-induced ACTH peaks were of longer duration than those after ACTH1-24 injection. The different depressor capacities of similar sized cortisol episodes and the lack of proportionality between spontaneous and provoked ACTH and cortisol peaks suggest that there are separate adrenocortical activation channels, which depend on the origin of the stimulation.

Neuroendocrine processes underlying ultradian sleep regulation in man.

Sleep is not a uniform state but is characterized by the cyclic alternation between rapid eye movement (REM) and non-REM sleep with a periodicity of 90-110 min. This cycle length corresponds to one of the oscillations in electroencephalographic (EEG) activity in the delta frequency band (0.5-3.5 Hz), which reflect the depth of sleep. To demonstrate the intimate link between EEG and neuroendocrine rhythmic activities in man, we adopted a procedure permitting simultaneous analysis of sleep EEG activity in the delta band and of two activating systems: the adrenocorticotropic system and the autonomic nervous system. Adrenocorticotropic activity was evaluated by calculating the cortisol secretory rate in blood samples taken at 10-min intervals. Autonomic activity was estimated by two measures of heart rate variability: 1) by the ratio of low-frequency (LF) to high-frequency (HF) power from spectral analysis of R-R intervals; and 2) by the interbeat autocorrelation coefficient of R-R intervals (rRR intervals between two successive cardiac beats). The results revealed that oscillations in delta wave activity, adrenocorticotropic activity, and autonomic activity are linked in a well-defined manner. Delta wave activity developed when cortisol secretory rates had returned to low levels and sympathetic tone was low or decreasing, as reflected by a low LF/HF ratio and by low levels in rRR. Conversely, the decrease in delta wave activity occurred together with an increase in the LF/HF ratio and in rRR. REM sleep was associated with a decrease in cortisol secretory rates preceding REM sleep onset, whereas the LF/HF ratio and rRR remained high. These results demonstrate a close coupling of adrenocorticotropic, autonomic, and EEG ultradian rhythms during sleep in man. They suggest that low neuroendocrine activity is a prerequisite for the increase in slow wave activity.

Cortisol secretion is related to electroencephalographic alertness in human subjects during daytime wakefulness.

To determine whether human hypothalamo-pituitary-adrenal axis activity is related to the alertness level during wakefulness, 10 healthy young men were studied under resting conditions in the daytime (0900-1800 h) after an 8-h nighttime sleep (2300-0700 h). A serial 70-sec gaze fixation task was required every 10 min throughout the daytime experimental session. The corresponding waking electroencephalographic (EEG) segments were submitted to quantitative spectral analysis, from which EEG beta activity (absolute power density in the 13-35 Hz frequency band), an index of central alertness, was computed. Blood was collected continuously through an indwelling venous catheter and sampled at 10-min intervals. Plasma cortisol concentrations were measured by RIA, and the corresponding secretory rates were determined by a deconvolution procedure. Analysis of individual profiles demonstrated a declining tendency for EEG beta activity and cortisol secretory rate, with an overall temporal relationship indicated by positive and significant cross-correlation coefficients between the two variables in all subjects (average r=0.565, P < 0.001). Changes in cortisol secretion lagged behind fluctuations in EEG beta activity, with an average delay of 10 min for all the subjects. On the average, 4.6+/-0.4 cortisol secretory pulses and 4.9+/-0.5 peaks in EEG beta activity were identified by a detection algorithm. A significant, although not systematic, association between the episodes in the two variables was found: 44% of the peaks in EEG beta activity (relative amplitude, near 125%; P < 0.001) occurred during an ascending phase of cortisol secretion, cortisol secretory rates increasing by 40% (P < 0.01) 10-min after peaks in EEG beta activity. However, no significant change in EEG beta activity was observed during the period from 50 min before to 50 min after pulses in cortisol secretion. In conclusion, the present study describes a temporal coupling between cortisol release and central alertness, as reflected in the waking EEG beta activity. These findings suggest the existence of connections between the mechanisms involved in the control of hypothalamo-pituitary-adrenal activity and the activation processes of the brain, which undergoes varying degrees of alertness throughout daytime wakefulness.

Circadian and ultradian variations of leptin in normal man under continuous enteral nutrition: relationship to sleep and body temperature.

To determine the influence of circadian rhythmicity and sleep on the 24-h leptin diurnal variations, plasma leptin levels were measured at 10-min intervals over 24 h in seven normal subjects, once during nocturnal sleep, and once after an 8-h shift of sleep. The subjects were submitted to constant conditions (continuous enteral nutrition and bed rest in controlled chambers). Body temperature and plasma glucose and insulin levels were measured simultaneously. During nighttime sleep, leptin levels increased to a maximum (109.9 +/- 2.5% of the 24-h mean) and then decreased to reach a nadir in the late afternoon. The mean diurnal variation was 18.0 +/- 3.8% of the 24-h mean. In the daytime sleep condition, leptin levels rose during the night of deprivation to a maximum of 104.7 +/- 2.3% of the 24-h mean, decreased to a minimum around 0700 h, and then rose again during diurnal sleep (108.4 +/- 3.1% of the 24-h mean); the mean diurnal variation was 13.4 +/- 3.6% of the 24-h mean. ANOVA revealed a significant interaction between time of day and sleep effects (P < 0.05). The diurnal and the sleep-related variations of plasma leptin mirrored those of body temperature and roughly paralleled those of plasma glucose and insulin; the amplitudes of the diurnal leptin variations were significantly correlated with the amplitudes of the diurnal body temperature variations (P < 0.05). Plasma leptin levels also displayed irregular pulses of low amplitude (mean duration, 70 min) that were not affected by sleep, but were associated with a significant decrease in glucose and insulin levels (P < 0.01). These results demonstrate that under continuous enteral nutrition, plasma leptin levels are modulated by both a slight circadian component and sleep, which interact under normal conditions, and suggest that leptin is implicated in circadian thermoregulatory adjustments.

Relationships between intact parathyroid hormone 24-hour profiles, sleep-wake cycle, and sleep electroencephalographic activity in man.

To determine whether the 24-h intact PTH (iPTH) profile is influenced by the sleep-wake cycle, and whether iPTH pulses show a temporal relationship with internal sleep structure, eight normal young men were studied during 24 h under basal conditions, once with normal nighttime sleep from 2300-0700 h and once after a night of sleep deprivation followed by an 8-h period of daytime sleep from 0700-1500 h. During the 8-h nighttime sleep period, mean iPTH levels were significantly increased by +13% and mean iPTH pulse amplitudes by +31% as compared with the 8-h subsequent waking periods. During the 8 h of total sleep deprivation, mean iPTH levels were not significantly different from the corresponding period in nighttime sleep condition, but mean iPTH pulse amplitudes were significantly lower (P < 0.01). The 8-h daytime sleep period was associated with increased mean iPTH levels and mean iPTH pulse amplitudes (+15% and +57%, respectively, as compared with the corresponding period in nighttime sleep condition). The number of pulses was similar in both experimental series and was not influenced by sleep or by time of day. Analysis of coincidence between iPTH pulses, plasma ionized calcium and plasma phosphate pulses, and slow wave sleep, as well as with rapid eye movement sleep episodes, did not reveal any significant association. Cross-correlation analysis between iPTH, plasma ionized calcium, and plasma phosphate fluctuations during sleep also showed no systematic association. Seven other subjects were studied during a nighttime sleep period in which temporal relationships between iPTH and internal sleep structure were reevaluated using spectral analysis of the sleep electroencephalogram. Cross-correlation analysis between iPTH levels and delta-relative power fluctuations showed nonsignificant results, which confirms the lack of relationship with slow wave sleep. This study demonstrates that the iPTH 24-h profile is influenced by sleep processes with a weak circadian component. However, iPTH pulses are not temporally linked with sleep electroencephalographic activity nor with calcemia and phosphatemia fluctuations. This evidence raises questions about the origin of iPTH pulses.

Ultradian oscillations in plasma renin activity: their relationships to meals and sleep stages.

The 24-h pattern of PRA was studied in 6 supine normal subjects, and the relationship between sleep stages and PRA oscillations was analyzed using 18 nighttime profiles and the concomitant polygraphic recordings of sleep. Blood was collected at 10-min intervals. The slow trends obtained by adjusting a third degree polynomial to the 24-h data were not reproducible among individuals, and no circadian pattern was detected. Sustained oscillations in PRA occurred throughout the day. Spectral analysis revealed that PRA oscillated at a regular periodicity of about 100 min during the night. This periodicity was modified during the daytime by meal intake, which induced PRA peaks with large interindividual variations in size. A close relationship was found between the nocturnal PRA oscillations and the alternance of rapid eye movement (REM) sleep and non-REM sleep. Non-REM sleep invariably coincided with increasing or peaking PRA levels. REM sleep occurred as PRA was declining or at nadirs. More precisely, increases in PRA marked the transition from REM sleep to stage II, whereas stages III and IV usually occurred when PRA was highest. This relationship between the periodic nocturnal oscillations in PRA and the alternance of the REM-non-REM cycles may translate a similar oscillatory process in the central nervous system or may be linked to hemodynamic changes during sleep that might be partly controlled by the renin-angiotensin system.

Oscillations in sympatho-vagal balance oppose variations in delta-wave activity and the associated renin release.

To determine the potential role of the sympathetic nervous system in the generation of the oscillations in PRA over the 24-h period, we used the autocorrelation coefficient of RR interval (rRR), a new tool to evaluate the sympatho-vagal balance continuously. We determined the influence of the sympathetic nervous system both on the nocturnal PRA oscillations associated to increases in delta-wave activity and on the daytime oscillations that occur randomly in awake subjects. PRA and rRR were determined every 10 min during 24 h in nine healthy subjects under continuous bed rest. Electroencephalographic spectral analysis was used to establish the variations in delta-wave activity during sleep, from 2300-0700 h. The overnight profiles in PRA, rRR and delta-wave activity were analyzed using a modified version of the pulse detection program ULTRA. The temporal link among the profiles of rRR, PRA, and delta-wave activity was quantified using cross-correlation analysis. During sleep, large oscillations in PRA were strongly linked to variations in delta-wave activity. They were preceded by opposite oscillations in rRR, decreases in rRR reflecting predominant vagal activity, and increases in rRR reflecting sympathetic dominance. During the waking periods, the levels of rRR were higher, with smaller variations. The daytime PRA oscillations were not associated with any significant changes in rRR, and conversely, significant oscillations in rRR were not followed by any significant changes in PRA. In conclusion, the sympathetic nervous system is not directly involved in the generation of renin oscillations observed under basal conditions. During sleep, the oscillations in sympatho-vagal balance are inversely related to the variations in delta-wave activity and the associated renin release. The processes that give the intermittent signal for concomitant increases in slow wave activity and renin release from the kidney remain to be identified.

Modulation of episodic renin release during sleep in humans.

We previously described a strong concordance between nocturnal oscillations in plasma renin activity and sleep cycles. To examine whether modifying renal renin content or release influences the response to central stimuli linked to sleep stage alternation, plasma renin activity was measured every 10 minutes from 11:00 PM to 8:00 AM in three groups of six subjects. The first group received one 40 mg dose of the diuretic furosemide; the second group underwent the night experiment after 3 days on a low sodium diet; the third group received one 100 mg dose of the beta-blocker atenolol. Each subject underwent a control night when a placebo was given. The nocturnal curves were analyzed with a pulse detection program. For the control nights, 74 of the 83 sleep cycles were associated with significant plasma renin activity oscillations; non-rapid eye movement sleep occurred in the ascending portions and rapid eye movement sleep in the declining portions of the oscillations. These oscillations persisted in the three groups of subjects during the experimental nights and the relation with the sleep stages was not disturbed. Acute stimulation by furosemide amplified the oscillations and led to a general upward trend of the nocturnal profiles. Similarly, a low sodium diet, which led to a slow increase in renal renin content, provoked large oscillations with high initial levels. However, in both cases the mean relative amplitude of the oscillations, expressed as a percentage of the nocturnal means, was similar to that of the control nights and approximated 60%.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-four-hour profiles of plasma renin activity in relation to the sleep-wake cycle.

OBJECTIVE: To evaluate the relative contribution of sleep and the endogenous circadian rhythmicity in producing the 24-h variations in the plasma renin activity. METHODS: Ten normal young men were studied, under basal conditions with normal nocturnal sleep from 2300-0700 h and once after a night of total sleep deprivation followed by 8 h daytime sleep from 0700 to 1500 h. Plasma renin activity was measured every 10 min for 24 h and the profiles were analysed using the pulse detection program ULTRA. RESULTS: During the 8 h night-time sleep a significant increase in the mean plasma renin activity levels occurred compared with the subsequent 8-h waking periods. After the shift in the sleep period, a sleep-associated increase was clearly apparent during the daytime hours. The number of the amplitude of the oscillations, linked to the non-rapid eye movement-rapid eye movement sleep cycles, increased during sleep (at whatever time it occurred), and were dependent on the regularity and the length of the sleep cycles. In awake subjects the plasma renin activity generally fluctuated in a more damped and irregular manner, but occasionally the plasma renin activity oscillated at a regular periodicity with two dominant peaks centred around 100 and 50 min. CONCLUSION: These results demonstrate that the 24-h plasma renin activity variations are not circadian in nature but are related to sleep processes, which create the nycthemeral rhythm by increasing both the frequency and the amplitude of the oscillations.

Obstructive sleep apnea treatment: peripheral and central effects on plasma renin activity and aldosterone.

To assess the effect of obstructive sleep apnea treatment on plasma renin activity (PRA) and plasma aldosterone seven male patients were studied under two conditions: untreated and treated with nasal continuous positive airways pressure (CPAP). PRA and plasma aldosterone were measured at 10-min intervals for both nights. CPAP treatment diminished the urinary and Na+ excretion, whereas plasma volume increased. The mean levels of PRA and aldosterone were significantly enhanced by the treatment, increasing respectively from 1.5 +/- 0.3 to 3.0 +/- 0.7 ngAI ml-1.hr-1 (p less than 0.05) and from 8.0 +/- 1.0 to 12.0 +/- 1.7 ng.100 ml-1 (p less than 0.05). PRA curves reflected the overall sleep structure as similarly described in normal subjects. The apnea-induced sleep disturbance led to flat PRA profiles and the restoration of a normal sleep pattern by treatment restored the PRA oscillations related to the sleep cycles and consequently restored aldosterone oscillations. The mean amplitude of these oscillations increased respectively from 1.0 +/- 0.1 to 1.8 +/- 0.4 ngAI ml-1.hr-1 and from 5.4 +/- 1.2 to 10.9 +/- 1.9 ng.100 ml-1. These results suggest that CPAP treatment modifies the nocturnal patterns of PRA and aldosterone by increasing their mean levels and their oscillation amplitude. This indicates increased secretion, which contributes to the normalization of urine and Na output.

Comparative effect of night and daytime sleep on the 24-hour cortisol secretory profile.

To determine whether cortisol secretion interacts with daytime sleep in a similar manner to that reported for night sleep, 14 healthy young men were studied during two 24-hour cycles. During one cycle they slept during the night, during the other the sleep period was delayed by 8 hours. Secretory rates were calculated by a deconvolution procedure from plasma cortisol, measured at 10-minute intervals. The amount of cortisol secreted during night sleep was lower than during the corresponding period of sleep deprivation (12.7 +/- 1.1 vs. 16.3 +/- 1.6 mg; p < 0.05), but daytime sleep beginning at the habitual time of morning awakening failed to inhibit cortisol secretion significantly. There was no difference between the amount of cortisol secreted from 0700 to 1500 hours in sleeping subjects and in subjects who were awake during the same period of time (24.2 +/- 1.5 vs. 22.5 +/- 1.4 mg). Even if the comparison between sleeping and waking subjects was restricted to the period 0700-1100 hours or 0700-0900 hours, no significant difference was found. Neither secretory pulse amplitude nor frequency differed significantly in either period. However, detailed analysis of the secretory rates in day sleepers demonstrated a transient decrease in cortisol secretion at about the time of sleep onset, which began 10 minutes before and lasted 20 minutes after falling asleep. Spontaneous or provoked awakenings had a determining influence on the secretory profiles. Ten to 20 minutes after awakening from either night or day sleep cortisol secretion increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)