Altered Orcadian Rhythms of Blood Pressure and Heart Rate in Non-Hemodialysis Chronic Renal Failure

The extended use of ambulatory monitoring has permitted the identification of many conditions in which the circadian rhythm of blood pressure is altered. The common denominator seems to be an impairment of the autonomic nervous system function. We examined whether the circadian blood pressure rhythm is altered in chronic renal failure (where autonomic dysfunction is usually present) by using a standardized chronobiological inferential statistical method in hospitalized subjects. For this purpose, a group of 30 non-hemodialysis hypertensive patients with chronic renal failure was compared with a second group of 30 patients affected by uncomplicated mild-to-moderate essential hypertension. The two groups were matched by age, sex and circadian mesors of blood pressure. Diet, meal times, sleep and activity logs were standardized. Blood pressure and heart rate recordings were obtained by using an automatic oscillometric recorder and subsequently analyzed according to the cosinor method. A mean circadian rhythm of blood pressure was documented in both groups, but while the mean acrophases occurred between 2 and 3 p.m. in essential hypertension, in renal failure they were between 11 p.m. and midnight for blood pressure and around 7 p.m. for heart rate. In addition, the mean circadian amplitudes were significantly lower in renal failure, while the mean circadian mesor of heart rate was significantly higher. Our data demonstrate that the circadian rhythms of blood pressure and heart rate are altered also in hypertension due to chronic renal failure.     

Altered Orcadian Rhythms of Blood Pressure and Heart Rate in Non-Hemodialysis Chronic Renal Failure

The extended use of ambulatory monitoring has permitted the identification of many conditions in which the circadian rhythm of blood pressure is altered. The common denominator seems to be an impairment of the autonomic nervous system function. We examined whether the circadian blood pressure rhythm is altered in chronic renal failure (where autonomic dysfunction is usually present) by using a standardized chronobiological inferential statistical method in hospitalized subjects. For this purpose, a group of 30 non-hemodialysis hypertensive patients with chronic renal failure was compared with a second group of 30 patients affected by uncomplicated mild-to-moderate essential hypertension. The two groups were matched by age, sex and circadian mesors of blood pressure. Diet, meal times, sleep and activity logs were standardized. Blood pressure and heart rate recordings were obtained by using an automatic oscillometric recorder and subsequently analyzed according to the cosinor method. A mean circadian rhythm of blood pressure was documented in both groups, but while the mean acrophases occurred between 2 and 3 p.m. in essential hypertension, in renal failure they were between 11 p.m. and midnight for blood pressure and around 7 p.m. for heart rate. In addition, the mean circadian amplitudes were significantly lower in renal failure, while the mean circadian mesor of heart rate was significantly higher. Our data demonstrate that the circadian rhythms of blood pressure and heart rate are altered also in hypertension due to chronic renal failure.     

Autorhythmometry in hypertension: some methodological aspects and clinical implications

Autorhythmometry of blood pressure is a technique easy to be performed and well accepted by hypertensive patients. A simple inspection of data self-collected 5 times a day for many days constitute a sufficiently reliable automonitoring of blood pressure both in basal conditions and in relation to the efficacy of some dietary and/or pharmacological treatment. Several examples are reported to show that more sophisticated statistical manipulation of the data collected may give rise to a better understanding of some clinical and physiological aspects. Both analysis of variance, performed on individual subsets of data averaged at each sampling hour, and single cosinor, performed on longitudinal time series, may be used to detect and quantify a circadian rhythm as a systematic daily variation, averaging towards zero the noise superimposed to the actual time series. Serial section analysis of the data, along all the experimental span, is useful to detect a) the reproducibility of the rhythm b) the variation of its parameters induced by changes in the experimental conditions c) the long-term trend. In the first subject the influence on the circadian rhythm of the pulse rate, temperature and blood pressure, due to a 4 h advancing shift in the rest-activity synchronizer, is well documented. In the first hypertensive patient a circadian rhythm is demonstrated also in blood pressure during two non-consecutive months. No difference is detected in both mesor and amplitude of blood pressure and a full resynchronization of the acrophase is achieved when a 1 h delaying shift in the rest activity synchronizer is imposed. In the second patient a well reproducible rhythm of systolic blood pressure and a low noise/signal ratio is documented by the serial section display. In the third patient the 'lability' of hypertention seems mainly due to salt sensitivity, as documented by the significant lowering of the mesor in the second experimental span, when a lowering of only 30 mEq/day in salt intake is imposed. The serial section better documents the salt-sensitivity of this patient, during a span when loading and depressing of salt intake is imposed. In the last patient the prompt effect of therapy in lowering blood pressure within normal range is well documented by serial section with 3 day interval. A possible effect of masking the circadian rhythm of blood pressure, due to therapy, is inferred by the serial section display with an interval of the same length (33 days) as the subspan without therapy. The possibility of prevention in the hypertensive disease is discussed, with the aim of autorhythmometry and statistical methods employed in this paper.     

Diurnal rhythm of the total antioxidant activity of saliva of children with chronic viral hepatitis

The diurinal rhythms of a total antioxidant activity of a saliva were investigated depending on activity of the inflammatory process in a liver of children with chronic virus hepatitis HBV and HCV. The circadian rhythms were found desynchronized, which was showed in lowering of the mesor value, oscillations amplitude, and a rhythm inversion and transformation, as an additional biorhythmological criterion of the presence of the chronic hepatitis of a viral etiology. A tendency of a circadian rhythm to remain with a daily acrophasis but with a law level of amplitude oscillations and a mesor was to be observed after the treatment of children with inactive HBV. By an active HBV a circadian rhythm with it's inversion has been renewed. It was determined the remaining of an ultradian rhythm with increasing level of amplitude oscillations after the treatment of inactive HCV. The law amplitude oscillations and a insignificant increasing of a meror level were characteristic for the circadian rhythm of total AOA of the children with active HBV. It was proved the possibility of usage of the biorhythmological parameters of diurinal rhythms of total AOA as a criteria of efficiency of the conducted therapy for the given group with disease children.     

Serum angiotensin-converting enzyme activity in pre-eclamptic pregnancy: evidence for a relative hypermesorACEemia

The circadian rhythm of serum angiotensin-converting enzyme (ACE) activity was investigated in pregnant women with normal and pre-eclamptic gestation. The chronobiological approach was able to document the occurrence of a circadian rhythm for serum ACE activity in normal pregnancy. Such a rhythm is characterized by a decreased mesor and amplitude and a shifted crest. The circadian rhythm for serum ACE activity was not detectable in pre-eclamptic pregnancy. Such an abrogation is accompanied by a negligible decrease of mesor suggesting the occurrence of a relative hyperACEemia. This disorder could play a role in pregnancy-induced hypertension.     

Circadian Rhythm of Blood Pressure and Heart Rate in Cardiopathic Patients Before and After Heart Transplantation

The aim of this study was to investigate the natural history of the circadian rhythm of blood pressure (BP) and heart rate (HR) in 10 patients with heart failure (class IV of the New York Heart Association), who underwent heart transplantation because of primary congestive cardiomyopathy. The control group was 10 age-matched clinically healthy subjects. The BP and HR monitor-ings were performed before and after transplantation. Preoperatively, analysis of variance and cosinor methods validated the occurrence of a statistically significant BP and HR circadian rhythm in cardiopathic patients. Over the 4 days after surgery, both the cosinor method and serial section analysis were unable to validate a 24-h periodicity for BP and HR in patients with heart transplants. Six months after surgery, the BP and HR circadian rhythm was not detected as well. One year after transplantation. the BP and HR circadian rhythm was statistically validated. The recovery of the BP and HR circadian rhythm 1 year after heart transplantation can be regarded as a clinical sign of a reacquired susceptibility to neurovegetative chronoregulation.     

Metabolic cycles are linked to the cardiovascular diurnal rhythm in rats with essential hypertension

Background

The loss of diurnal rhythm in blood pressure (BP) is an important predictor of end-organ damage in hypertensive and diabetic patients. Recent evidence has suggested that two major physiological circadian rhythms, the metabolic and cardiovascular rhythms, are subject to regulation by overlapping molecular pathways, indicating that dysregulation of metabolic cycles could desynchronize the normal diurnal rhythm of BP with the daily light/dark cycle. However, little is known about the impact of changes in metabolic cycles on BP diurnal rhythm.

Methodology/Principal Findings

To test the hypothesis that feeding-fasting cycles could affect the diurnal pattern of BP, we used spontaneously hypertensive rats (SHR) which develop essential hypertension with disrupted diurnal BP rhythms and examined whether abnormal BP rhythms in SHR were caused by alteration in the daily feeding rhythm. We found that SHR exhibit attenuated feeding rhythm which accompanies disrupted rhythms in metabolic gene expression not only in metabolic tissues but also in cardiovascular tissues. More importantly, the correction of abnormal feeding rhythms in SHR restored the daily BP rhythm and was accompanied by changes in the timing of expression of key circadian and metabolic genes in cardiovascular tissues.

Conclusions/Significance

These results indicate that the metabolic cycle is an important determinant of the cardiovascular diurnal rhythm and that disrupted BP rhythms in hypertensive patients can be normalized by manipulating feeding cycles.     

Mice Show Circadian Rhythms of Blood Pressure During Each Wake-Sleep State

A daily rhythm of blood pressure (BP), with maximum values in the activity period, carries important prognostic information. The extent to which this rhythm depends on behavioral factors remains debated. Mice are the species of choice for functional genomics. In mice, episodes of wakefulness and sleep are not restricted to particular daily periods, allowing BP in each wake-sleep state to be measured at each time of day. The aim of this study was to investigate whether a circadian rhythm of BP is manifest in each wake-sleep state in mice. Mice with B6 genetic background (n?=?26) were implanted with a telemetric BP transducer and electrodes to discriminate wake-sleep states and recorded while housed under a 12:12?h light-dark period. For each mouse, 8 values of BP were obtained in each wake-sleep state (wakefulness, non-rapid-eye-movement sleep, and rapid-eye-movement sleep) by averaging over successive 3-h time bins. Analysis of variance evidenced a significant time effect in each wake-sleep state as well as a significant wake-sleep state?×?time interaction effect. In an additional group of mice (n?=?3) recorded in constant darkness, the Lomb-Scargle periodogram also revealed a significant circadian rhythm of BP in each wake-sleep state. These findings demonstrate that during each wake-sleep state, mice show daily and circadian rhythms of BP in conditions of entrainment to the light-dark cycle and in free-running conditions of constant darkness, respectively. (Author correspondence: giovanna.zoccoli@unibo.it)     

Daily variations of plasma sex hormone-binding globulin binding capacity, testosterone and luteinizing hormone concentrations in healthy rested adult males

In this study the daily variations of plasma sex hormone-binding globulin (SHBG) binding capacity were measured together with plasma testosterone and luteinizing hormone (LH) concentrations in 7 healthy rested adult males. Plasma SHBG-binding capacity demonstrated a significant circadian rhythm (acrophase = 2.06 p.m.; mesor = 0.35 +/- 0.6 ng testosterone bound/100 ml; amplitude = 17% of the mesor). Plasma testosterone also showed a circadian rhythm (acrophase = 7.02 a.m.; mesor = 4.38 +/- 0.67 ng/ml; amplitude = 18% of the mesor). The free testosterone index (or the ratio between plasma testosterone and SHBG-binding capacity) was not correlated with plasma LH levels. In our hands this last parameter did not vary according to a circadian pattern. These data are discussed in terms of a feedback mechanism controlling the pituitary-testis axis regulation.     

Role of the liver in the regulation of circadian rhythm of blood iron in rats]

In experiments with Wistar rats there was discovered statistically significant circadian rhythm of serum iron concentration reaching its maximum in the evening, minimum--early in the morning, and having an amplitude of at least 20% of the mesor. The reciprocal interrelations between circadian cycles of iron content in blood and liver were also found. The synchronization of blood iron level with lipid peroxidation products in membranous liver structures, as well as serum alanine aminotransferase activity, and their inversion with respect to the circadian rhythms of liver RES absorption ability and liver iron content are considered to be a proof of liver participation in regulation of iron exchange temporal organization in rats.     

Repeated assessment of the endogenous 24-hour profile of blood pressure under constant routine

The impact of environmental and behavioral factors on the 24-h profile of blood pressure (BP) has been well established. Various attempts have been made to control these exogenous factors, in order to investigate a possible endogenous circadian variation of BP. Recently, we reported the results of the first environmentally and behaviorally controlled laboratory study with 24-h recordings of BP and heart rate (HR) during maintained wakefulness. In this constant-routine study, a pronounced endogenous circadian rhythm of HR was found, but circadian variation of BP was absent. This result suggested that the circadian rhythm of BP observed in earlier controlled studies, with sleep allowed, was evoked by the sleep-wake cycle as opposed to the endogenous circadian pacemaker. In order to verify our previous finding during maintained wakefulness, we repeated the experiment five times with six normotensive, healthy young subjects. Statistical analyses of the hourly measurements of BP and HR confirmed the replicable presence of an endogenous circadian rhythm of HR, as well as the consistent absence of an endogenous circadian variation of BP. Thus, this study provided additional evidence that the 24-h profile of BP—as observed under normal circumstances—is the sole result of environmental and behavioral factors such as the occurrence of sleep, and has no endogenous circadian component. (Chronobiology International, 18(1), 85-98, 2001)     

Postnatal development of TRH and TSH rhythms in the rat

We previously observed that under a 12-hour light/12-hour dark schedule (lights off at 19.00 h), adult male Sprague-Dawley rats showed a circadian rhythm for serum thyroid-stimulating hormone (TSH) with a zenith near midday. In the present work, the ontogenesis of serum TSH rhythm was determined as well as pituitary TSH variations. In addition, hypothalamic and blood TRH were measured in these rats aged 15, 25, 40 and 70 days when sacrificed. As from the first age studied (15 days), a hypothalamic thyrotropin-releasing hormone (TRH) circadian rhythm was present. The mesor and the amplitude of this hypothalamic TRH rhythm increased while the rats were growing up, in contrast with the decrease observed for these parameters as far as blood TRH circadian rhythm is concerned. The time of the acrophase moved from 17.32 h in the 15-day-old rats to 13.57 h in the 70-day-old rats, being constantly in phase opposition with the blood TRH acrophase. The low amplitude pituitary TSH circadian rhythm detected in the young rat disappeared in the adult while, in contrast, the serum TSH rhythm became consistent to reach the well-characterized circadian midday peak in the 70-day-old rats.     

Circannual variation in human erythrocyte adenosine aminohydrolase

In serially independent samples of blood from apparently healthy subjects controlled as to clock-hour of blood withdrawal but not as to any circannual changes in circadian state, human erythrocyte adenosine aminohydrolase undergoes a statistically significant circannual rhythm, which may or may not be aliased. This rhythm is also demonstrated in patients with a variety of neoplastic diseases and it occurs around a statistically significantly lower mesor in patients with a variety of malignant tumors investigated.     

REPEATED ASSESSMENT OF THE ENDOGENOUS 24-HOUR PROFILE OF BLOOD PRESSURE UNDER CONSTANT ROUTINE*

The impact of environmental and behavioral factors on the 24-h profile of blood pressure (BP) has been well established. Various attempts have been made to control these exogenous factors, in order to investigate a possible endogenous circadian variation of BP. Recently, we reported the results of the first environmentally and behaviorally controlled laboratory study with 24-h recordings of BP and heart rate (HR) during maintained wakefulness. In this constant-routine study, a pronounced endogenous circadian rhythm of HR was found, but circadian variation of BP was absent. This result suggested that the circadian rhythm of BP observed in earlier controlled studies, with sleep allowed, was evoked by the sleep–wake cycle as opposed to the endogenous circadian pacemaker. In order to verify our previous finding during maintained wakefulness, we repeated the experiment five times with six normotensive, healthy young subjects. Statistical analyses of the hourly measurements of BP and HR confirmed the replicable presence of an endogenous circadian rhythm of HR, as well as the consistent absence of an endogenous circadian variation of BP. Thus, this study provided additional evidence that the 24-h profile of BP—as observed under normal circumstances—is the sole result of environmental and behavioral factors such as the occurrence of sleep, and has no endogenous circadian component. (Chronobiology International, 18(1), 85–98, 2001)     

Role of Sleep Restriction in Daily Rhythms of Expression of Hypothalamic Core Clock Genes in Mice

Lack of sleep time is a menace to modern people, and it leads to chronic diseases and mental illnesses. Circadian processes control sleep, but little is known about how sleep affects the circadian system. Therefore, we performed a 28-day sleep restriction (SR) treatment in mice. Sleep restriction disrupted the clock genes’ circadian rhythm. The circadian rhythms of the Cry1 and Per1/2/3 genes disappeared. The acrophase of the clock genes (Bmal1, Clock, Rev-erbα, and Rorβ) that still had a circadian rhythm was advanced, while the acrophase of negative clock gene Cry2 was delayed. Clock genes’ upstream signals ERK and EIFs also had circadian rhythm disorders. Accompanied by changes in the central oscillator, the plasma output signal (melatonin, corticosterone, IL-6, and TNF-α) had an advanced acrophase. While the melatonin mesor was decreased, the corticosterone, IL-6, and TNF-α mesor was increased. Our results indicated that chronic sleep loss could disrupt the circadian rhythm of the central clock through ERK and EIFs and affect the output signal downstream of the core biological clock.     

Diurnal variations of serum beta 2-microglobulin in multiple myeloma

The chronobiological circadian behaviour in serum levels of beta 2-microglobulin has been investigated in three groups of subjects: (A) 6 healthy controls; (B) 6 patients with untreated multiple myeloma; (C) 6 patients with multiple myeloma in complete remission after polychemotherapy. From all subjects, under the same standard life conditions, venous blood samples were drawn at 4-hour intervals starting from midnight during the span of a whole day. Circulating serum beta 2-microglobulin levels were determined by RIA method. The time-related data were analyzed by chronograms and the "mean-group cosinor" method. A significant circadian rhythm for serum beta 2-microglobulin was detected in the control group, with a peak in the morning hours, and in untreated patients, with a peak in the afternoon hours. No significant rhythm was found in treated patients with multiple myeloma. A significant mesor reduction was noted in patients with complete remission, correlated with the absence of circadian rhythm, in respect to untreated patients. These data suggest that serum levels of beta 2-microglobulin could be related to the neoplastic plasma cell proliferation and to the effect of therapy, and that the circadian evaluation could be used as a guide in monitoring myeloma patients.     

Atrial Natriuretic Peptide and Circadian Blood Pressure Regulation: Clues from a Chronobiological Approach

A critical review of the data available in the literature today permits a better understanding of the multiple actions of atrial natriuretic peptide (ANP) on the cardiovascular system. Moreover, the results of chronobiological studies suggest a role for this peptide in the determination of the circadian rhythm of blood pressure (BP). ANP can affect BP by several mechanisms, including modification of renal function and vascular tone, counteraction of the renin-angiotensin-al-dosterone system, and action on brain regulatory sites. A series of interrelated events may follow from very small changes in the plasma levels of ANP. The endpoints are blood volume and BP reduction, but they are rapidly offset (mainly by reactive sympathetic activation) as soon as blood volume or pressure is thredtened. The circadian rhythms of BP and ANP are antiphasic under normal conditions and in essential hypertension. The loss in the nocturnal decrease of BP is accompanied by a comparable loss in the nocturnal surge of ANP in hypertensive renal failure and hypotensive heart failure. In the latter condition, BP and ANP variabilities correlate significantly both before and after therapy-induced functional recovery, independently of the mean BP levels. Autonomic function modulates the secretion of ANP, which seems more apt to determine only transient changes in BP levels, as suggested by the short half-life of the peptide and the buffering role of its clearance receptors. There is now sufficient evidence that ANP contributes to short-term control over BP and electrolyte balance, in contrast and in opposition to the renin-angiotensin-aldosterone system, which is involved primarily in long-term BP control. By interfering with other well-established neu-rohormonal factors, ANP appears to be an additional modulator of the circadian rhythm of BP.     

Ten-Year-Replicated Circadian Profiles for 36 Physiological,Serological and Urinary Variables in Healthy Men

At 3-hr intervals over a 24-hr span, 36 systemic, serologic and urinary variables were examined in 7 men in their mid 20's in the Spring of 1969, and again in the same 7 men in the Spring of 1979 under a similar chronobiologic protocol, using the same chemical and numerical analytical procedures. The variables examined for rhythms by cosinor were: vital signs—blood pressure (systoliC., diastoliC., pulse pressure and mean arterial pressure), heart rate, intraocular pressure (left and right), oral temperature; serum components—albumin, albumin/globulin ratio, total bilirubin, calcium, carbon dioxide, chlorides, bilirubin, cholesterol, globulin, glucose, potassium, sodium, sodium/potassium ratio, transaminase, triglycerides, total protein, urea nitrogen; and urine components—calcium, calcium/magnesium ratio, creatinine, magnesium, pH, potassium, sodium, sodium/potassium ratio, urea clearance, urea nitrogen, volume and zinc. Although all subjects appeared clinically healthy in 1969 and in 1979, certain inter-study differences were observed in a number of rhythm parameters of different variables. Statistically significant increases in mesor for the group as a whole were observed forserum Ca, cholesterol, Cl, CO₂, K, Na, and while statistically significant mesor decreases for a group as a whole were noted in serum glucose and transaminase. Statistically significant increases in amplitude for the group as a whole were observed in serum chloride and urinary Na/K ratio, while statistically signficiant decreases were observed in amplitude for blood pressure, heart rate, serum albumin, A/G ratio, globulin, glucose, protein, sodium and transaminase. For the group as a whole, a statistically significant advance in acrophase was observed in serum transaminase, while a statistically significant delay in acrophase was observed for serum A/G ratio, globulin, glucose, potassium, protein, sodium and for urinary magnesium. Statistically significant by sign test, but not by cosinor, was a numerical mesor increase for urinary urea clearance, a numerical decrease in mesor for urinary zinc; a numerical amplitude decrease for serum cholesterol; and a numerical delay in acrophase for oral temperature and serum cholesterol, CO², and globulin in all men examined. Only mesor changes in serum cholesterol and urinary Ca/Mg were positively correlated with the change in body size over the 10-year span between studies.

From a circadian chronobiologic perspective, the immense amount of data uniquely reviewed in this report across a 10-year span in seven healthy individuals serves a useful beginning to the study of the effects of normal aging upon commonly measured physiologic and biochemical variables and, more importantly, upon the circadian rhythm characteristics of these variables. A great deal of supposition about what happens to the mesor, amplitude and acrophase of an individual's circadian rhythms in a variety of endpoints has been based upon transverse studies of short duration and relatively few longterm studies. The further accumulation of data such as presented here and similar long-term longitudinal time series can have no adequate substitute for truly understanding whether reproducible age-related changes in circadian rhythms occur as individuals age.

With these qualifications and with the further qualification that the timing of our observations within the aging process (mid-20's and mid-30's) may be suboptimal for conclusions about aging, very interesting trends definitely appear worth comment. There is some evidence in these data that the flattening of circadian rhythms may really accompany advancing age. In grouped data, this fall in amplitude may be secondary to an isolated fall in predictable swing around the mesor or a combination of this and increased variability of the acrophase with or without amplitude changes. The data are not robust enough to be sure of the relative contribution of these two components. In any event, the circadian amplitude of each and every physiologic variable studied demonstrated a tendency to fall between the mid-20's and mid- 30's. This tendency toward a flattening of circadian variability is also a very prominent property of many of the serum chemistries which were measured. The circadian patterns of excretion of substances in the urine change much less between the mid-20's and mid-30's in our subjects. These findings may indicate a separate effect of aging especially upon metabolic hepatic variables and upon nephrologic circadian rhythms. Cardiovascular rhythms seem to change more in parallel with hepatic metabolic rhythms in contradistinction to the kidney-related serum and urinary rhythms.

Further, ongoing statistical analyses may hopefully turn up interesting and relevant cross-correlations among the individual data themselves in each study year and between the 10-year span, as well as with rhythm (mesor, amplitude and acrophase) and other physiologic characteristics of each subject. Planned re-observation of what happens to the circadian time structure of these seven individuals in their mid-40's will prove invaluable to further sorting out of the effects of aging upon circadian time structure.     

Mice show circadian rhythms of blood pressure during each wake-sleep state

A daily rhythm of blood pressure (BP), with maximum values in the activity period, carries important prognostic information. The extent to which this rhythm depends on behavioral factors remains debated. Mice are the species of choice for functional genomics. In mice, episodes of wakefulness and sleep are not restricted to particular daily periods, allowing BP in each wake-sleep state to be measured at each time of day. The aim of this study was to investigate whether a circadian rhythm of BP is manifest in each wake-sleep state in mice. Mice with B6 genetic background (n?=?26) were implanted with a telemetric BP transducer and electrodes to discriminate wake-sleep states and recorded while housed under a 12:12?h light-dark period. For each mouse, 8 values of BP were obtained in each wake-sleep state (wakefulness, non-rapid-eye-movement sleep, and rapid-eye-movement sleep) by averaging over successive 3-h time bins. Analysis of variance evidenced a significant time effect in each wake-sleep state as well as a significant wake-sleep state?×?time interaction effect. In an additional group of mice (n?=?3) recorded in constant darkness, the Lomb-Scargle periodogram also revealed a significant circadian rhythm of BP in each wake-sleep state. These findings demonstrate that during each wake-sleep state, mice show daily and circadian rhythms of BP in conditions of entrainment to the light-dark cycle and in free-running conditions of constant darkness, respectively.     

Comparison of the circadian rhythm in cell proliferation in corneal epithelium of male rats studied under normal and hypobaric (hypoxic) conditions

Groups of 20-45-day-old rats maintained on a light (0600-1800)/dark (1800-0600) regimen with food and water available ad libitum were studied for the effect of hypoxic hypoxia on the circadian rhythm of corneal epithelial mitosis and thymidine incorporation. In experiments conducted during the months of September and November, hypoxic hypoxia was accomplished by the exposure of rats to a simulated altitude of 7500 m in one series of experiments, or to a gaseous mixture of 8% oxygen and 92% nitrogen at sea level atmospheric pressure (760 mmHg) in another series of experiments. Controls were included as well. Statistically significant (P less than 0.05) circadian rhythmicity in the corneal mitotic index was substantiated in the control animals with mesor (M) = 12.4%, amplitude (A) = 9.6% and acrophase (phi) of 0911. In the hypoxic hypoxia situation, the mesor and amplitude were depressed to 8.6 and 5.9%, respectively. In control groups, thymidine incorporation was circadian rhythmic with M = 38.5 and A = 11.3 cpm/microns DNA and acrophase of 2255. In the hypoxic hypoxia situation, the mesor was similar to the controls; whereas the amplitude was suppressed to 6.1% and acrophase was phase advanced by about 7 hr. Changes in the circadian rhythm of corneal mitosis and in thymidine incorporation under hypoxic hypoxia can be explained by programmed-in-time energy requirements during the corneal cell regeneration cycle.