M. Follenius

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 and 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.

Effect of short-term endurance training on exercise capacity, haemodynamics and atrial natriuretic peptide secretion in heart transplant recipients

Exercise tolerance of heart transplant patients is often limited. Central and peripheral factors have been proposed to explain such exercise limitation but, to date, the leading factors remain to be determined. We examined how a short-term endurance exercise training programme may improve exercise capacity after heart transplantation, and whether atrial natriuretic peptide (ANP) release may contribute to the beneficial effects of exercise training by minimizing ischaemia and/or cardiac and circulatory congestion through its vasodilatation and haemoconcentration properties. Seven heart transplant recipients performed a square-wave endurance exercise test before and after 6 weeks of supervised training, while monitoring haemodynamic parameters, ANP and catecholamine concentrations. After training, the maximal tolerated power and the total mechanical work load increased from 130.4 (SEM 6.5) to 150.0 (SEM 6.0) W (P < 0.05) and from 2.05 (SEM 0.1) to 3.58 (SEM 0.14) kJ · kg−1 (P < 0.001). Resting heart rate decreased from 100.0 (SEM 3.4) to 92.4 (SEM 3.5) beats · min−1 (P < 0.05) but resting and exercise induced increases in cardiac output, stroke volume, right atrial, pulmonary capillary wedge, systemic and pulmonary artery pressures were not significantly changed by training. Exercise-induced decrease of systemic vascular resistance was similar before and after training. After training arterio-venous differences in oxygen content were similar but maximal lactate concentrations decreased from 6.20 (SEM 0.55) to 4.88 (SEM 0.6) mmol · 1−1 (P < 0.05) during exercise. Similarly, maximal exercise noradrenaline concentration tended to decrease from 2060 (SEM 327) to 1168 (SEM 227) pg · ml−1. A significant correlation was observed between lactate and catecholamines concentrations. The ANP concentration at rest and the exercise-induced ANP concentration did not change throughout the experiment [104.8 (SEM 13.1) pg · ml−1 vs 116.0 (SEM 13.5) pg · ml−1 and 200.0 (SEM 23.0) pg · ml−1 vs 206.5 (SEM 25.9) pg · ml−1 respectively]. The results of this study suggested that the significant improvement in exercise capacity observed after this short-term endurance training period may have arisen mainly through peripheral mechanisms, associated with the possible decrease in plasma catecholamine concentrations and reversal of muscle deconditioning and/or prednisone-induced myopathy.

Nocturnal plasma thyrotropin variations are related to slow‐wave sleep

SUMMARY  The thyrotropin (TSH) nycthemeral pattern is known to be strongly influenced by sleep, but previous studies have failed to demonstrate any link between sleep structure and TSH variations. Using 10‐min blood sampling, nocturnal TSH profiles were analysed in 24 young healthy subjects during normal sleep. Six of the subjects then underwent a partial sleep deprivation experiment, sleep was permitted from 03.00 hours to 07.00 hours. Descending slopes of TSH values were observed for the first 20 minutes of SWS episodes, whereas no significant trend was found for other sleep stages. During the period of sleep deprivation, nocturnal TSH levels increased and then declined immediately after sleep onset; however, the association between SWS and descending TSH slopes persisted. This temporal concordance suggests that some particular mechanisms associated with SWS may modulate TSH release, or conversely that increasing TSH levels prevent the occurrence of SWS.

Postprandial oscillations of plasma glucose, insulin and C-peptide in man

SummaryPostprandial plasma glucose, insulin and C-peptide profiles were studied in eight normal subjects, in the afternoon or in the evening. Two to five synchronous oscillations, with a mean period of 51 to 112 min were detected. The oscillations were highest after meals and were then damped, reverting to fasting levels after up to 340 min. Additional short-term oscillations, with periods of 20–30 min and 9–14 min, were observed. Cross-correlation studies of glucose and insulin and of insulin and C-peptide revealed a high correlation in the frequency bands considered. The synchronous oscillations of insulin and C-peptide suggest cyclic variations in pancreatic secretion rather than cyclic changes in insulin degradation.

Ultradian plasma corticotropin and cortisol rhythms: time-series analyses

Abstract24-h plasma patterns of ACTH and cortisol were established in 6 subjects who had standard meals and in 4 subjects under continuous enterai nutrition. Temporal relationships between both hormones were analyzed. The individual assay data were subjected to time-series analyses to identify the periods of the oscillations in the plasma levels. The spontaneously occurring cortisol peaks were preceded by increases in ACTH levels, but z-score transformations clearly revealed that ACTH and cortisol were not quantitatively linked throughout the day. Individual subjects’ power spectra gave evidence of a predominant periodicity in the oscillations of both hormones. These periodicities varied between individuals. They were 55–140 min for ACTH and 95–180 min for cortisol, indicating that, on occasion, a single cortisol peak may be initiated by two ACTH peaks. Cross spectral analysis of the individual data gave coherence spectra with a large peak which accounted for a substantial concordance of their period length, and cross variance spectra showed a consistent phase relationship between both hormones. These time series analyses applied to the data further support the concept that ACTH is the stimulating factor of cortisol release under basic conditions.

The influence of the initial state of hydration on endocrine responses to exercise in the heat

SummaryThis study examines the effect of the initial state of hydration on hormone responses to prolonged exercise in the heat. Five subjects at two initial hydration levels (hypohydrated and hyperhydrated) were exposed to a 36°C environment for 3 h of intermittent exercise. During exercise, the subjects were either fluid-deprived, or rehydrated with water or an isotonic electrolyte sucrose solution (ISO). Both the stress hormones, adrenocorticotropic hormone and cortisol, and the main fluid regulatory hormones, aldosterone, renin activity (PRA) and arginine vasopressin (AVP), were measured in blood samples taken every hour. Prior hyperhydration significantly reduced initial AVP, aldosterone and PRA levels. However, except for AVP, which responded to exercise significantly less in previously hyperhydrated subjects (p<0.05), the initial hydration state did not influence the subsequent vascular and hormonal responses when the subjects were fluid-deprived while exercising. Concurrent rehydration, either with water or with ISO, reduced or even abolished the hormonal responses. There were no significant differences according to the initial hydration state, except for PRA responses, which were significantly lower (p<0.01) in previously hyperhydrated subjects who also received water during exercise. These results indicate that prior hydration levels influence only slightly the hormonal responses to prolonged exercise in the heat. Progressive rehydration during exercise, especially when extra electrolytes are given, is more efficient in maintaining plasma volume and osmolarity and in reducing the hormonal responses.

Growth Hormone Secretion in Night Workers

We previously reported that, in night workers, cortisol and TSH rhythms, known to have a high endogenous component, adapted only partially to the nocturnal schedule. The aim of the present study was to investigate the degree of adaptation of the growth hormone (GH) rhythm, considered to be mainly sleep-dependent, but for which a weak circadian drive has also been suggested. Eleven night workers were studied during their usual sleep-wake cycle, and two groups of 11 normally day-active subjects, sleeping once during the night and once after an 8-h sleep delay, were used as control groups. GH secretory rates were calculated by deconvolution of the plasma concentrations analyzed at 10-min intervals. The total amount of GH secreted during the 24 h did not differ between the three groups and the main secretory episode occurred, in most cases, during the first half of the sleep period. In night sleepers and night workers the enhanced amount of GH secreted at that time was followed by a significantly lower amount secreted during the second part of the sleep period (p < 0.001 and p < 0.05, respectively). For night sleepers, an enhanced GH pulse frequency was found at the beginning of sleep, whereas for night workers and day sleepers the pulses were distributed more randomly throughout the nychthemeron. After an abrupt sleep shift, all the subjects displayed a GH pulse at the usual time of early sleep, but such a pulse was present in only 8 of 11 night workers. Thus the amount of GH secreted between 23:00 h and 03:00 h in day sleepers did not differ significantly from that observed in night sleepers, whereas it differed for night workers. These results confirm the considerable influence of sleep in driving the GH rhythm and the existence of a circadian influence revealed by an acute shift in the sleep period. They also provide evidence of an incomplete adjustment of GH rhythms in night workers.

Temporal relationships between pulsatile cortisol secretion and electroencephalographic activity during sleep in man

A temporal link between slow wave sleep and low or decreasing cortisol release has been previously demonstrated. This relationship was re-evaluated in 15 healthy male subjects using spectral analysis of their sleep electroencephalogram (EEG). EEG activity in the delta, theta, alpha and beta bands was cross-correlated with cortisol secretory rates at 10-min intervals. For the period of pulsatile cortisol secretion, an inverse relationship was found with the delta band with an average cross-correlation coefficient of -0.505 (P < 0.0001). Variations in cortisol secretory rates coincided with or anticipated opposite variations in delta wave activity by 10 or 20 min. A significant positive correlation was found with theta activity, but alpha and beta bands did not elicit any systematic association with cortisol profiles. These results demonstrate a temporal association between cortisol secretory pulses and delta wave activity in man, suggesting the existence of a central control common to both variables.

Temporal link between plasma thyrotropin levels and electroencephalographic activity in man

Plasma thyrotropin (TSH) levels have been previously shown to be associated with the internal sleep structure determined by conventional scoring of sleep stages. This temporal relationship was re-evaluated using spectral analysis of the sleep electroencephalogram (EEG). Eight healthy male subjects underwent two randomized night studies after having received either placebo or 5 mg ritanserin, a selective 5-HT2 receptor antagonist known to increase slow-wave sleep. Delta relative power and TSH levels, determined at 10 min intervals, were found to be inversely related with an average cross-correlation coefficient highly significant (P < 0.0001) in both experimental conditions. Alpha slow-wave index, an estimator of awakenings, and TSH pulses exhibited a significant temporal association in both conditions. These results demonstrate that TSH fluctuations are linked to the sleep EEG activity in man.

Nycthemeral patterns of thyroid hormones and their relationships with thyrotropin variations and sleep structure

In order to precise the relationships between TSH, FT3, and FT4 nycthemeral variations and the relationships between thyroid hormone variations and sleep, 8 healthy young males were studied twice, once during a 24-h experiment with normal nocturnal sleep, and once during a night of sleep deprivation. The subjects received continuous enteral nutrition and remained supine during the whole experiment. Blood was sampled every 10 min for TSH, FT3, and FT4 measurements. Thyroid hormones exhibited small oscillations which were not systematically related to TSH pulses, and there was no evidence of a nycthemeral rhythm. SWS was associated with TSH declining phases, whereas awakenings were strongly associated with ascending phases of TSH variations. There was no association between sleep structure or awakenings and thyroid hormones. Sleep deprivation led to increased TSH and FT3 levels, without any variation in FT4 levels. These results demonstrate that shortterm thyroid hormone variations do not only depend on the effect of TSH on thyroid secretion but also on a possible role of TSH on peripheral FT4 to FT3 conversion. Conversely, the relationships between TSH and SWS or awakenings are not mediated by thyroid hormones.