Comparative Studies on the Orcadian Rhythm of Corticosterone Lipid and Cholesterol Levels in Adrenals and Blood of Rats

The time-dependent relationship of corticosterone, lipids and cholesterol over a 48-hr period was studied in the adrenals and blood of rats. In addition an attempt was made to determine whether there was a reciprocal dependence among these compounds and also a correlation between corticosterone and cholesterol in the adrenals and blood.

Corticosterone and cholesterol exhibit a circadian rhythm in the adrenals and blood. The same is true for lipids in the serum. A reciprocal dependence between the compounds in the adrenals and blood could not be demonstrated. Only the time-dependent processes of the corticosterone content in the adrenals and plasma are well correlated with each other. High levels of these steroids in the adrenals are associated with high levels of these steroids in the plasma and vice versa.

An inverse correlation between corticosterone and cholesterol exists in the adrenals and in blood. Maximal levels of corticosterone correspond to minimal levels of cholesterol and vice versa.     

Variability in the Period of the Blood Pressure Orcadian Rhythm in Human Beings

In studies and assessments of human beings done in natural settings, it is assumed that the period τ of circadian rhythms, including ones of systolic (SBP) and diastolic (DBP) blood pressure, is equal to 24 hours. To test this hypothesis, SBP and DBP rhythms were studied in 112 medication-free, non-hospitalized subjects (62 males, 47.1 + 2.0 years [χ ± SEM], and 50 females, 54.5 ± 2.1 years) by 48h ambulatory blood pressure monitoring (ABPM). Of these, 26 were hypertensive (diurnal SBP> 140 mmHg and diurnal DBP> 90 mmHg) and 86 normotensive. All subjects were synchronized by their habitual daytime activities from ?08:00h to ?23:00h ± lh and by sleep at night. The BP was assessed at 15-minute intervals during a continuous 48h span using a Spacelabs model #90207 ABPM. The time series data of each subject were individually evaluated by power spectra analysis for the prominent x of the SBP and DBP rhythms. The prominent X differed from 24 hours in 22/112 subjects for SBP and in 16/112 subjects for DBP. Generally, in these individuals the τ was less than 24 hours. The occurrence of non-24h τ's was more frequent in hypertensive than normotensive subjects; the difference between the groups in the distribution of the prominent τ's by class (τ = 24h, >=12, 12h<24h, etc.) was statistically significant (χ² test =19.1; p < 0.001). No difference in the distribution of x's of blood pressure was detected according to the subject's age and gender. These findings suggest that ABPM done only for a duration of 24h may be too short to characterize accurately the features of the day-night variation in human BP, including the precise period of its rhythm. (Chronobiology International, 14(3), 307–317, 1997)     

Development of Adrenocortical Cyclic Nucleotide (Cyclic AMP and Cyclic GMP) and Corticosterone Orcadian Rhythms in Male and Female Rats

The daily rhythm of the adrenocortical cyclic nucleotides (cyclic AMP and cyclic GIMP) was studied in infant male and female Wistar rats before and after the establishment of an adult-like daily rhythm of plasma corticosterone. As in this strain the rhythm of corticosterone is known to be present on postnatal day 18, pups of 2 and 3 weeks of age were studied. The dams and the pups as well as the young adult animals were kept on a controlled 12L-12D photoperiod. Groups of 8-10 pups were killed at 4-hr intervals throughout the day. Plasma corticosterone levels and adrenal cyclic AMP and cyclic GMP concentrations were simultaneously measured and the daily patterns established. Pups of 2 weeks of age showed neither plasma corticosterone nor adrenal cyclic AMP rhythms whereas pups of 3 weeks of age exhibited a typical adult-like circadian rhythm for both variables. The patterns for adrenal cyclic GMP differed according to sex: In female pups no cyclic GMP circadian rhythm could be detected at either 2 or 3 wk. In male pups of 3 wk a typical mature rhythm for adrenal cyclic GMP was evident whereas in younger male pups (2 wk) a circadian rhythm was detected. This circadian rhythm, however, differed from mature circadian rhythm in that its peak was located at 1300 hr instead of 0700 hr. These results demonstrate that, unlike that of cyclic AMP the adrenal cyclic GMP circadian rhythm does not appear at the same time as the plasma corticosterone circadian rhythm. Moreover, a circadian rhythmicity for adrenal cyclic GMP can be found in the absence of any corticosterone circadian rhythm. These facts argue against the view of cyclic GMP being a mediator of ACTH-stimulated steroidogenesis.     

Development of Adrenocortical Cyclic Nucleotide (Cyclic AMP and Cyclic GMP) and Corticosterone Orcadian Rhythms in Male and Female Rats

The daily rhythm of the adrenocortical cyclic nucleotides (cyclic AMP and cyclic GIMP) was studied in infant male and female Wistar rats before and after the establishment of an adult-like daily rhythm of plasma corticosterone. As in this strain the rhythm of corticosterone is known to be present on postnatal day 18, pups of 2 and 3 weeks of age were studied. The dams and the pups as well as the young adult animals were kept on a controlled 12L-12D photoperiod. Groups of 8–10 pups were killed at 4-hr intervals throughout the day. Plasma corticosterone levels and adrenal cyclic AMP and cyclic GMP concentrations were simultaneously measured and the daily patterns established. Pups of 2 weeks of age showed neither plasma corticosterone nor adrenal cyclic AMP rhythms whereas pups of 3 weeks of age exhibited a typical adult-like circadian rhythm for both variables. The patterns for adrenal cyclic GMP differed according to sex: In female pups no cyclic GMP circadian rhythm could be detected at either 2 or 3 wk. In male pups of 3 wk a typical mature rhythm for adrenal cyclic GMP was evident whereas in younger male pups (2 wk) a circadian rhythm was detected. This circadian rhythm, however, differed from mature circadian rhythm in that its peak was located at 1300 hr instead of 0700 hr. These results demonstrate that, unlike that of cyclic AMP the adrenal cyclic GMP circadian rhythm does not appear at the same time as the plasma corticosterone circadian rhythm. Moreover, a circadian rhythmicity for adrenal cyclic GMP can be found in the absence of any corticosterone circadian rhythm. These facts argue against the view of cyclic GMP being a mediator of ACTH-stimulated steroidogenesis.     

Disorders of Orcadian Body Temperature Rhythm in Severely Brain-Damaged Patients

Twenty-four hour patterns of body temperature (BT) were recorded during consecutive 3-10 day spans from 14 severely brain-damaged patients. Seven patients exhibited a normal circadian BT rhythm with an amplitude of more than 1°C and a normal phase position of the minimum BT being observed during the latter half of the nocturnal sleep. One patient with a dispersed type of sleep exhibited an extremely low amplitude of the BT rhythm with mean average 0.69°C. In this patient, an 24-hr observation span was insufficient to detect the existence of a BT rhythm. Two patients manifested disturbance of period. As acrophase of the BT rhythm varied from day to day, the standard deviation (S.D.) of mean acrophase wasextremely large. For these patients the light-dark cycle did not act as an entrainer because both had visual disturbance. A phase advance of the minimum BT was observed in four patients. The minimum BT appeared in the first half of nocturnal sleep. These three disturbances (amplitude, period and phase), were revealed only by longitudinal observation of the BT rhythm, indicating the importance of long-term observations over a sufficient period to make the nature of the rhythm disturbances clear. These disturbances were not related to that of the sleep-wake cycle, as two patients showed normal circadian BT rhythm in spite of their dispersed-type sleep.     

Seasonal Variation in the Orcadian Rhythm of Pulmonary Function in Stable Astthmatic Children who have Nearly Outgrown their Asthma

To study whether nocturnal bronchial obstruction changes during the year, we assessed the circadian FEV₁ variation during four consecutive seasons in 20 children (12 boys; aged 9–12 years) with episodic asthma who were outgrowing their asthma. FEV₁ was determined every 4 h between 10:00 and 10:00 during two consecutive days. The last six FEV₁ values were submitted to cosinor and coefficient of variation (CV) analyses. The seasonal means (SD) in the group 24 h percent predicted FEV₁ was 85.5 (11.4), 81.2 (10.6), 86.0 (11.6), and 82.2 (14.0)% during spring, summer, autumn, and winter, respectively. The difference between the summer and autumn FEV₁ values was statistically significant (p < 0.05). The mean (SD) of the circadian amplitude values was 4.1 (4.3), 6.0 (3.8), 4.9 (3.4), and 7.2 (4.1)% during spring, summer, autumn, and winter, respectively. The difference in amplitude between the spring and winter and between the autumn and winter values was statistically significant (p<0.05). CV values of 48 of the 80 (60%) circadian FEV, time series exceeded the average CV of 5% observed in non-asthmatic children studied in our laboratory. There was an unequal distribution during the year in elevated CV values; 6, 17, 10, and 15 of the high CV values occurred, respectively, in the spring, summer, autumn, and winter. These results suggest that nocturnal bronchial obstruction may change seasonally in terms of severity and amplitude in children who have nearly outgrown their asthma. (Chronobiology International, 13(4), 295–303, 1996)     

Orcadian Rhythm in the Torque Developed by Elbow Flexors During Isometric Contraction Effect of Sampling Schedules

Time-dependent changes in elbow flexion torque have been documented according to two different sampling schedules. Seven physical education students took part in the first series of experiments, and 7 other similar subjects in the second. In both sets of experiments, the subjects performed isometric contractions: maximal and submaximal at 90° in the first experiments and maximal at different angular positions in the second. After a 30-minute rest period, the torque developed was measured at 00:00, 06:00, 09:00, 12:00, 15:00, 18:00, and 21:00h on the day of the experiment. These subjects remained in the laboratory for 24h. In the second series of experiments, the torque developed was measured at 01:00, 05:00, 09:00, 13:00, 17:00, and 21:00h over the subsequent 6 days with only one test session per day. In this case, there was an interval of 20h between two successive test sessions. In the first experiment, a significant time-of-day effect was observed for the torque of the elbow flexors under isometric conditions with an acrophase at 17:58h. The 24h normalized mean score was 92.85% with an amplitude of 7.63% of the daily mean. In the second series of experiments, there was evidence of a circadian rhythm in the torque developed by the elbow flexors at every angle position, especially at 90°, the angle investigated in the first set of experiments. The peak torque was calculated to have occurred at 17:55h. The amplitude of the rhythm was equal to 6.99% of the daily mean. There were no statistically significant differences in the characteristics of the circadian rhythm observed between the two experimental designs. We concluded that an experiment extending over several days could be employed to evaluate circadian rhythms in muscular activity reliably. (Chronobiology International, 14(3), 287–294, 1997)     

Orcadian Rhythm of Serotonin Binding in Rat Brain—I. Effect of the Light-Dark Cycle

High affinity serotonin binding to rat brain membranes showed a circadian rhythm with minimal binding at 1000 and a maximal binding at 0000. Brain serotonin levels were almost inverse to the rhythm of serotonin binding. Under reverse light-dark conditions, lights on from 1900 to 0700, a significant phase shift in serotonin binding and concentration of about 8-10 hr was found. The adaptation of the rats to the inverse light-dark cycle was ascertained by plasma ACTH and corticosterone assay.     

Effect of Escapable and Inescapable Stress on Levels of Catecholamines in Adrenals and Corticosterone in Blood Plasma in Young and Aged Rats

Effect of escapable and inescapable electrical stress (ES, IS) on the catecholaminergic system was studied in young (3 months) and aged (25 months) male Wistar rats on the day 3 after stress, using radioimmune analysis and high-pressure liquid chromatography. Catecholamine concentration in adrenals and corticosterone level in blood of control aged rats was lower than in young animals. On the third day after the electrical stimulation in cages with current-conducting floor, production of hormones of adrenal cortical and medullar layers rose significantly in aged rats, with a more pronounced increase of noradrenaline after IS, while of blood adrenaline and corticosterone, after ES. In young rats no significant changes in catecholamines were revealed, whereas the blood corticosterone level was increased after IS. Thus, in aged rats, a low basal level of catecholamines and corticosterone and a delayed stress response can be established. In old animals after ES, a long post-action was observed, which was quite comparable with the results obtained after IS in the both age groups.     

Effects of Amlodipine on Orcadian Rhythms in Blood Pressure,Heart Rate,and Motility: A Telemetric Study in Rats

In male Wistar rats [light (L): 07:00–19:00 h, dark (D): 19:00–07:00 h], the effects of the calcium channel blocker amlodipine (1, 3, 10 mg/kg i.p.) on blood pressure, heart rate, and motor activity were studied by telemetric monitoring. Amlodipine was injected either at 07:00 h or at 19:00 h. Systolic and diastolic blood pressure were dose-dependently decreased with more pronounced effects in the dark span, ED₅₀ values in D were about seven times lower than in L. In contrast, the dose-dependent increase in heart rate was more pronounced in L than in D. No significant effects of amlodipine were found on motor activity. The study gives evidence for a circadian phase-dependency in the cardiovascular effects amlodipine in rats.     

Effects of Amlodipine on Orcadian Rhythms in Blood Pressure, Heart Rate, and Motility: A Telemetric Study in Rats

In male Wistar rats [light (L): 07:00-19:00 h, dark (D): 19:00-07:00 h], the effects of the calcium channel blocker amlodipine (1, 3, 10 mg/kg i.p.) on blood pressure, heart rate, and motor activity were studied by telemetric monitoring. Amlodipine was injected either at 07:00 h or at 19:00 h. Systolic and diastolic blood pressure were dose-dependently decreased with more pronounced effects in the dark span, ED₅₀ values in D were about seven times lower than in L. In contrast, the dose-dependent increase in heart rate was more pronounced in L than in D. No significant effects of amlodipine were found on motor activity. The study gives evidence for a circadian phase-dependency in the cardiovascular effects amlodipine in rats.     

Circadian Rhythm of Blood Pressure: Internal and External Time Triggers

Diurnal blood pressure (BP) fluctuations are superimposed by a 24-h rhythm with usually lower levels during the night and higher levels during the day. In contrast to other rhythmic bioparameters, the diurnal BP rhythm is largely dependent on activity and sleep rather than on clock time. This has been demonstrated by the BP characteristics after shifted sleeping and working phases, during transition from sleep to wakefulness, and by the influence of sleep and activities on the 24-h BP curve during normal daily routines. Whereas the circadian rhythm of BP is predominantly governed by external time triggers, endogenous rhythmic-ity can only be detected by time microscopic analysis or in conditions where effects of external time triggers are almost excluded.     

Circadian Rhythm of the Liver of Male Rats Pre-Treated with Phenobarbital—ii. Hexobarbital Sleeping Time and Lipids Content in Liver and Serum

The circadian rhythm of hexobarbital sleeping time and lipids content in liver and serum were studied in 226 male Sprague-Dawley rats pretreated daily at 0800-0900 with 70 mg/kg (study 1 or 3) or 50 mg/kg (study 2) phenobarbital (PB) orally for 7 days. Thereafter, eight (study 1) or five (study 2 and 3) rats each were studied at 4-hr intervals at 1000, 1400, 1800, 2200, 0200, 0600 and 1000 through the following day. The lighting schedule in the colony was 12:12 ± light:dark (light from 0600 to 1800). The hexobarbital sleeping times of PB-pretreated rats were generally shortened compared to the controls and no circadian rhythm was observed. PB-treatment increased slightly the liver content of cholesterol, and significantly that of triglycerides and phospholipids. Liver cholesterol and phospholipids showed circadian rhythms with peaks during the dark phase. No circadian rhythm of liver triglycerides existed. In serum, levels of triglycerides and phospholipids were slightly lowered by PB-treatment, while levels of cholesterol and beta-lipoprotein were not influenced. Serum values did not exhibit circadian rhythms.     

Heart Rate Orcadian Rhythm as a Biological Marker of Desynchronization in Major Depression: A Methodological and Preliminary Report

Heart rate (HR) was continuously monitored during successive 24-hr periods in 19 healthy subjects and 26 major depressed patients (DSM III-R). Recordings were performed after a 2-week wash-out period and the morningness or eveningness typology of each subject was determined. The chronobiological parameters and rhythm percentage (RP) were calculated by the single cosinor method from the smoothed HR curves of each subject. In normal subjects, HR follows a circadian rhythm (RP > 65%) with the lowest values at night. Morning type subjects have an earlier peak time (13:30) than evening type subjects (17:30). Major depressive patients were split into two groups; in the first one HR circadian rhythm was still present (RP > 63%) with a decrease in amplitude (24%) while in the second group, no circadian rhythm of HR could be detected (RP < 25%, decrease in amplitude > 70%). In the group of patients with a persisting HK circadian rhythm, no veritable phase advance was observed. Our results suggest that circadian HR rhythm, which can be easily studied with non-invasive methods, might represent a chronobiological marker of some depressions. Given the lag that exists between the rhythms of morning type and evening type subjects, our study also stresses the importance of taking into account this behavioural trait in chronobiological studies.     

血压昼夜节律特征及其分子调控机制

正常血压具有典型的昼夜节律特征。血压昼夜节律异常与高血压靶器官损害和心血管事件发生呈明显相关关系,是独立于血压水平的重要致病因素。血压昼夜节律的产生和维持与时钟基因的周期性表达有关。时钟基因bmal1、per2是体内生物钟系统运行的关键基因,其表达水平和节律变化直接调节血压的昼夜节律。     

血压昼夜节律特征及其分子调控机制

正常血压具有典型的昼夜节律特征。血压昼夜节律异常与高血压靶器官损害和心血管事件发生呈明显相关关系,是独立于血压水平的重要致病因素。血压昼夜节律的产生和维持与时钟基因的周期性表达有关。时钟基因bmal1、per2是体内生物钟系统运行的关键基因,其表达水平和节律变化直接调节血压的昼夜节律。     

The Expression of Locomotor Orcadian Rhythm in Female German Cockroach, Blattella Germanica (L.)

Fifteen percent of intact female German cockroaches (n = 13), Blattella germanica (L.) (Dictyoptera: Blattellidae), had weak free-running locomotor rhythmicity under 28°C and constant darkness conditions. However, 86% of ovariectomized females (n = 14) showed a strong free-running rhythm under the same conditions with a circadian period of 23.60 ± 0.15 h, similar to the male's period of 23.45±0.03 h. In addition, the locomotory activities occurred mainly during the subjective night under DD conditions as was the case in males. These results indicated that female locomotion was under the control of a circadian oscillator, which was masked by the existence of ovaries. This internal masking effect could be removed by the existence of males, but females had no effect on the locomotor pattern of another female. Since the male failed to entrain female locomotion, its role as a zeitgeber was excluded. That the locomotory pattern of the females still coincided with their reproductive cycle when exposed to male odor suggests that exposure to a male only partially removed the internal masking effects.     

人参皂甙Re对神经内分泌系统功能的影响

研究人参皂甙Re对神经内分泌系统的保护作用。采用高效液相色谱检测法测定水浸．束缚应激大鼠脑内单胺类递质和血清皮质酮的含量。水浸-束缚应激模型能使大鼠额叶、纹状体、下丘脑三个脑区的单胺类递质及其代谢产物（去甲肾上腺素、多巴胺、高香草酸、5-羟色胺、5．羟吲哚乙酸）和血清皮质酮的含量明显增高。预先给予人参皂甙Re（4．5和9mg／kg,ig）后均有不同程度的降低,并呈一定的量效关系。结果表明人参皂甙Re具有一定的神经保护作用。     

四种中草药抗白内障形成中晶状体脂类过氧化水平及脂类含量的变化

我们观察了中草药防治大鼠半乳糖性白内障形成中脂类含量的变化及脂类过氧化水平。结果表明,与正常晶状体相比,白内障晶状体中总脂类的含量明显降低,总胆固醇的含量及脂类过氧化水平明显升高,总脂类与总胆固醇之比明显下降。而同时分别用黄苓、石斛、菟丝子及玉蝴蝶四种中草药水煎剂灌胃的大鼠晶状体中,总胆类与总胆固醇的含量基本恢复至正常;脂类过氧化水平虽仍高于正常晶状体,但也明显低于白内障晶状体,表明脂类过氧化参与了白内障的形成,上述四种中草药具有抑制脂类过氧化的作用。