J. Saini

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.

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.

Growth hormone and prolactin response to rehydration during exercise: effect of water and carbohydrate solutions

SummaryThe effect of progressive rehydration with either water or a carbohydrate solution on the plasma growth hormone (GH) and prolactin (PRL) response to exercise was examined together with plasma somatostatin. Five subjects underwent four 3-h experimental sessions at 36°C in which 25-min exercise periods alternated with 5-min rest periods. The sessions were conducted without fluid replacement (DH) or under rehydration with either water or isosmotic carbohydrate solutions AISO (acid) or NISO (neutral). The fluid was given every 10 min after the 1st h of exercise. Plasma GH increased significantly (p < 0.01) under DH after 2 and 3 h of exercise; this increase was prevented by rehydration with water, AISO and NISO. Plasma glucose was significantly higher following AISO and NISO rehydration compared with DH. This possibly influenced the GH response, but there was no difference between plasma glucose levels under DH and water rehydration at any time. The solutions tended to attenuate the increase in heart rate, rectal temperature and plasma cortisol, suggesting that the lack of GH response under rehydration conditions is a result of decreasing physiological stress levels. The GH response could not be explained by plasma somatostatin, which tended to decline in all sessions. Plasma PRL did not increase in any of the sessions, confirming that exercise without rehydration is a more potent stimulator of GH than of PRL. It is concluded that progressive rehydration with water is sufficient to prevent the exercise-induced increase in plasma GH.

Training effects on the hydromineral endocrine responses of cardiac transplant patients

Cardiac transplant patients manifest several haemodynamic changes as well as altered peripheral responses to exercise which may disrupt body fluid regulation. This study examined the effect on an endurance training programme on the exercise-induced hydromineral endocrine responses of heart transplant patients. Seven patients underwent a square-wave exercise test before and after a 6-week training programme. The tests were performed at the same absolute intensity but, during training, the workload was increased to maintain the same relative exercise intensity. Pretraining results were compared to those obtained from agematched controls. Training improved physical capacity, producing a significant increase in maximal tolerated power and workload between the first and last training session (P < 0.05, P < 0.001, respectively). Haematocrit and osmolality were increased in both groups at the end of exercise (P < 0.01) but changes observed post-training did not differ from pretraining values. Apart from atrial natriuretic peptide (ANP), which showed significantly higher concentrations at rest and during exercise (P < 0.01), the changes in hydromineral hormones of the patients resembled those of the controls. Basal plasma renin activity (PRA) was slightly raised prior to training (P < 0.07) compared to the controls and post-training. For both PRA and aldosterone, a significant training effect was revealed when both the exercise-stimulated increase and postexercise decline were considered (P < 0.05), possibly reflecting lower noradrenaline concentrations. Training had no effect on either basal or exercise stimulated ANP levels, which is compatible with the theory that ANP regulation is largely under mechanical rather than sympathetic nervous system control. Mean arginine vasopressin concentrations in the patients were not increased, possibly due to inhibitory effects of immunosuppressive glucocorticoids combined with the large variation in response observed, particularly for the untrained patients. In summary, these results showed that despite cardiac denervation, the heart transplant patients demonstrated effective body fluid regulatory endocrine responses during exercise and that although training produced substantial improvement in their physical capacity, it was accompanied by only subtle changes in hydromineral hormones.

Influence of alcohol on the hydromineral hormone responses to exercise in a warm environment

Alcohol consumption at rest is associated with disturbed water and salt regulation reflected by changed responses in the hydromineral hormones. This study investigated the effect of alcohol on endocrine systems involved in body fluid and electrolyte regulation under conditions of physical exercise in the heat, a situation in which under normal circumstances, the hydromineral hormones are stimulated in an attempt to preserve physiological homeostasis. Eight healthy male volunteers participated in two trials, which differed only in the presence or absence of alcohol (1.2 g alcohol · kg−1 body mass) in a cocktail drink. After consuming the cocktail, the subjects exercised for 60 min on a cycle ergometer (45% maximal oxygen consumption) at 35°C. Compared to the control situation alcohol consumption (maximal plasma concentrations reaching about 1.08 g · l−1) produced an increase in body fluid loss (P < 0.05), but did not induce significant differences in plasma volume changes. Plasma volume decreased in both sessions during exercise (P < 0.01) and a significant rebound (P < 0.001) occurred during recovery. Osmolality was significantly higher (P < 0.001) during rest, exercise and recovery periods compared to the placebo trials, but no effect of alcohol on plasma Na+ and K+ concentrations was observed. In the alcohol test conditions, the arginine vasopressin (AVP) response to exercise was significantly dampened (P < 0.05). In contrast, alcohol had no effect on aldosterone or atrial natriuretic peptide (ANP). These results demonstrated that alcohol ingestion augmented body fluid losses due to a suppressive effect on AVP during physical exercise conducted in a warm environment. The increase in osmolality due to alcohol did not influence the aldosterone and ANP responses, which would suggest that total osmolality does not play a major role in the regulation of these hormones.

Effect of awakening on aldosterone

Overnight studies conducted in 10 male volunteers showed that the effect of awakening on aldosterone and its main regulatory hormonal systems depends on the time of its occurrence. Waking periods in the latter half of the night induced concomitant increases in plasma levels of aldosterone and ACTH, whereas plasma renin activity tended to decrease. No effect was apparent, when subjects were awoken during the first hours of sleep, which is known to be a quiescent period of adrenocorticotropic activity. These results provide evidence of the dominant influence of ACTH during the second half of the night insuring the regulation of aldosterone during waking periods.

Nocturnal prolactin pulses in relation to luteinizing hormone and thyrotropin.

The two hypothalamic releasing factors, luteinizing hormone releasing hormone (LHRH) and thyrotropin releasing hormone (TRH), have been shown to stimulate pituitary prolactin (PRL) release as well as their respective pituitary hormones, luteinizing hormone (LH) and thyrotropin (TSH). In this study the influence of LH and TSH regulatory mechanisms on nocturnal PRL secretion was investigated by evaluating whether the coincidence of PRL with LH and TSH pulses occurred more frequently than would be expected if the hormone generators were not coupled. Thirty night studies were conducted in twelve healthy male subjects. Six subjects underwent 3 studies and 6 subjects 2 studies. Blood was collected into aliquots at 10 min intervals throughout the night and plasma concentrations of PRL, TSH, and LH were determined. From the plasma profiles, hormone secretory rates were calculated using a method of deconvolution. Significant plasma and secretory hormone pulses were identified by a peak detection computer program. For statistical analysis the night studies of each subject were concatenated. Concomitance between the plasma pulses of both TSH and LH with PRL was insufficient to reject the null hypothesis of random coincidence. An increase in the number of subjects demonstrating significant coincidence between the hormone pulses was obtained when secretory pulses were analysed. Seven of the 12 and 10 of the 12 subjects showed significant concomitance between PRL and respectively TSH and LH. This proportion was sufficient to confirm copulsatility between PRL and LH. These results suggest that LH regulatory mechanisms are involved in the generation of the nocturnal pulsatile PRL profile, TRH may also play a role in the secretion of PRL at a central level, but was not reflected in the plasma or secretory profiles because of other overriding regulatory factors.

Clomipramine-induced sleep disturbance does not impair its prolactin-releasing action

The present study was undertaken to examine the role of sleep disturbance, induced by clomipramine administration, on the secretory rate of prolactin (PRL) in addition to the direct drug effect. Two groups of supine subjects were studied under placebo-controlled conditions, one during the night, when sleeping (n=7) and the other at daytime, when awake (n=6). Each subject received a single 50 mg dose of clomipramine given orally 2 hours before blood collection. Plasma PRL concentrations were analysed at 10 min intervals and underlying secretory rates calculated by a deconvolution procedure. For both experiments the drug intake led to significant increases in PRL secretion, acting preferentially on tonic secretion as pulse amplitude and frequency did not differ significantly from corresponding control values. During the night clomipramine ingestion altered the complete sleep architecture in that it suppressed REM sleep and the sleep cycles and induced increased wakefulness. As the relative increase in PRL secretion expressed as a percentage of the mean did not significantly differ between the night and day time studies (46±19% vs 34±10%), it can be concluded that the observed sleep disturbance did not interfere with the drug action perse. The presence of REM sleep was shown not to be a determining factor either for secretory pulse amplitude and frequency, as, for both, mean nocturnal values were similar with and without prior clomipramine ingestion.