Scaling the amplitudes of the circadian pattern of resting oxygen consumption, body temperature and heart rate in mammals

We questioned whether the amplitudes of the circadian pattern of body temperature (T(b)), oxygen consumption (V (O(2))) and heart rate (HR) changed systematically among species of different body weight (W). Because bodies of large mass have a greater heat capacitance than those of smaller mass, if the relative amplitude (i.e., amplitude/mean value) of metabolic rate was constant, one would expect the T(b) oscillation to decrease with the increase in the species W. We compiled data of T(b), V (O(2)) and HR from a literature survey of over 200 studies that investigated the circadian pattern of these parameters. Monotremata, Marsupials and Chiroptera, were excluded because of their characteristically low metabolic rate and T(b). The peak-trough ratios of V (O(2)) (42 species) and HR (35 species) averaged, respectively, 1.57+/-0.08, and 1.35+/-0.07, and were independent of W. The daily high values of T(b) did not change, while the daily low T(b) values slightly increased, with the species W; hence, the high-low T(b) difference (57 species) decreased with W (3.3 degrees C.W(-0.13)). However, the decrease in T(b) amplitude with W was much less than expected from physical principles, and the high-low T(b) ratio remained significantly above unity even in the largest mammals. Thus, it appears that in mammals, despite the huge differences in physical characteristics, the amplitude of the circadian pattern is a fixed (for V (O(2)) and HR), or almost fixed (for T(b)), fraction of the 24-h mean value. Presumably, the amplitudes of the oscillations are controlled parameters of physiological significance.     

Seasonal patterns of body temperature daily rhythms in group-living Cape ground squirrels Xerus inauris

Organisms respond to cyclical environmental conditions by entraining their endogenous biological rhythms. Such physiological responses are expected to be substantial for species inhabiting arid environments which incur large variations in daily and seasonal ambient temperature (T(a)). We measured core body temperature (T(b)) daily rhythms of Cape ground squirrels Xerus inauris inhabiting an area of Kalahari grassland for six months from the Austral winter through to the summer. Squirrels inhabited two different areas: an exposed flood plain and a nearby wooded, shady area, and occurred in different social group sizes, defined by the number of individuals that shared a sleeping burrow. Of a suite of environmental variables measured, maximal daily T(a) provided the greatest explanatory power for mean T(b) whereas sunrise had greatest power for T(b) acrophase. There were significant changes in mean T(b) and T(b) acrophase over time with mean T(b) increasing and T(b) acrophase becoming earlier as the season progressed. Squirrels also emerged from their burrows earlier and returned to them later over the measurement period. Greater increases in T(b), sometimes in excess of 5°C, were noted during the first hour post emergence, after which T(b) remained relatively constant. This is consistent with observations that squirrels entered their burrows during the day to 'offload' heat. In addition, greater T(b) amplitude values were noted in individuals inhabiting the flood plain compared with the woodland suggesting that squirrels dealt with increased environmental variability by attempting to reduce their T(a)-T(b) gradient. Finally, there were significant effects of age and group size on T(b) with a lower and less variable T(b) in younger individuals and those from larger group sizes. These data indicate that Cape ground squirrels have a labile T(b) which is sensitive to a number of abiotic and biotic factors and which enables them to be active in a harsh and variable environment.     

Daily rhythms of Fos expression in hypothalamic targets of the suprachiasmatic nucleus in diurnal and nocturnal rodents.

Little is known about the differences in the neural substrates of circadian rhythms that are responsible for the maintenance of differences between diurnal and nocturnal patterns of activity in mammals. In both groups of animals, the suprachiasmatic nucleus (SCN) functions as the principal circadian pacemaker, and surprisingly, several correlates of neuronal activity in the SCN show similar daily patterns in diurnal and nocturnal species. In this study, immunocytochemistry was used to monitor daily fluctuations in the expression of the nuclear phosphoprotein Fos in the SCN and in hypothalamic targets of the SCN axonal outputs in the nocturnal laboratory rat and in the diurnal murid rodent, Arvicanthis niloticus. The daily patterns of Fos expression in the SCN were very similar across the two species. However, clear species differences were seen in regions of the hypothalamus that receive inputs from the SCN including the subparaventricular zone. These results indicate that differences in the circadian system found downstream from the SCN contribute to the emergence of a diurnal or nocturnal profile in mammals.     

Circadian and seasonal changes of the inducer:suppressor ratio (OKT4+:OKT8+) in venous blood of healthy adults

Circadian and seasonal variations in the T helper: T suppressor-cytotoxic ratio were investigated in peripheral blood from five healthy young men. Mononuclear cells were isolated on Ficoll-Paque gradient, then incubated with OKT4 and OKT8 monoclonal antibodies. Plasma cortisol was determined in four of these seven time series. Large interindividual differences were documented and statistically validated for the 24-hr.-means of total lymphocytes, OKT4+:OKT8+ ratio, and of plasma cortisol (both total and free). For a pooled data, a circadian rhythm was demonstrated by cosinor (p less than 0.001) for total lymphocytes (acrophase at 1.00 hr.), total plasma cortisol (acrophase at 10.30 hrs.) and free plasma cortisol (acrophase at 9.50 hrs.), but not for OKT4+:OKT8+ ratio. This index however exhibited a statistically significant circadian rhythm in April and August, but not in November. Its double-amplitude exceeded 80% of the 24-hour-mean and its acrophase was localized at 6.40 hrs. in April and at 22.30 hrs. in August. Its 24-hr-mean was higher in August as compared to April and November. The circadian rhythm in the OKT4+:OKT8+ ratio did not seem to be related to that of plasma cortisol. Both circadian and seasonal variations need to be taken into account when investigating the regulations of immune variables such as T helper: T suppressor-cytotoxic ratio.     

Plasma Corticosterone, Motor Activity and Metabolic Circadian Patterns in Streptozotocin-Induced Diabetic Rats

Experiments were conducted in male rats to study the effects of streptozotocin-induced diabetes on circadian rhythms of (a) plasma corticosterone concentrations; (b) motor activity; and (c) metabolic patterns. Animals were entrained to LD cycles of 12: 12 hr and fed ad libitum.

A daily rhythm of plasma corticosterone concentrations was found in controls animals with peak levels at 2400 hr and low values during the remaining hours. This rhythm was statistically confirmed by the cosinor method and had an amplitude of 3.37μg/100 ml and the acrophase at 100 hr. A loss of the normal circadian variation was observed in diabetic animals, with a nadir at the onset of light period and high values throughout the remaining hours; cosinor analysis of these data showed no circadian rhythm, delete and a higher mean level than controls.

As expected, normal rats presented most of their motor activity during the dark period with 80+ of total daily activity; the cosinor method demonstrated a circadian rhythm with an amplitude of 60+ of the mean level and the acrophase at 0852 hr. Both diabetic and control rats showed a similar activity during the light phase, but diabetic animals had less activity than controls during the night and their percentage of total daily activity was similar in both phases of the LD cycle (50+ for each one). With the cosinor method we were able to show the persistence of a circadian rhythm in the motor activity of diabetic rats, but with a mesor and amplitude lower than in controls (amplitude rested at 60+ of the mean level) and its acrophase advanced to 0148 hr.

The metabolic activity pattern of diabetic rats also changed: whereas controls showed a greater metabolic activity during the night (70+ food; 82+ water; 54+ urine; 67+ faeces), diabetics did not show differences between both phases of the LD cycle. Water ingested and urine excreted by the diabetic group were higher than normal during light and dark periods; food consumed and faeces excreted were higher than controls only in the light phase.

These data suggest that alterations in circadian rhythms of plasma corticosterone and motor activity are consecutive to the loss of the feeding circadian pattern, due to polyphagia and polydipsia showed by these animals, which need to extend intakes during the light and dark phases.     

Hibernation and circadian rhythms of body temperature in free-living Arctic ground squirrels

In mammals, the circadian master clock generates daily rhythms of body temperature (T(b)) that act to entrain rhythms in peripheral circadian oscillators. The persistence and function of circadian rhythms during mammalian hibernation is contentious, and the factors that contribute to the reestablishment of rhythms after hibernation are unclear. We collected regular measures of core T(b) (every 34 min) and ambient light conditions (every 30 s) before, during, and following hibernation in free-living male arctic ground squirrels. Free-running circadian T(b) rhythms at euthermic levels of T(b) persisted for up to 10 d in constant darkness after animals became sequestered in their hibernacula in fall. During steady state torpor, T(b) was constant and arrhythmic for up to 13 d (within the 0.19°C resolution of loggers). In spring, males ended heterothermy but remained in their burrows at euthermic levels of T(b) for 22-26 d; patterns of T(b) were arrhythmic for the first 10 d of euthermia. One of four squirrels exhibited a significant free-running T(b) rhythm (τ = 22.1 h) before emergence; this squirrel had been briefly exposed to low-amplitude light before emergence. In all animals, diurnal T(b) rhythms were immediately reestablished coincident with emergence to the surface and the resumption of surface activity. Our results support the hypothesis that clock function is inhibited during hibernation and reactivated by exposure to light, although resumption of extended surface activity does not appear to be necessary to reinitiate T(b) cycles.     

Rhythms in human bone marrow and blood cells

In 24h studies of bone marrow (BM), circadian stage-dependent variations were demonstrated in the proliferative activity of BM cells from subsets of 35 healthy diurnally active men. On an average, the percentage of total BM cells in deoxyribonucleic acid (DNA) synthesis phase was 188% greater at midday than at midnight (circadian rhythm: p = 0.018; acrophase or peak time of 13: 16h). Patients with malignant disease (n = 15) and a normal cortisol circadian rhythm showed higher fractions of BM cells in S-phase at midday. Colony-forming units--granulocyte/macrophage (CFU-GM), an indicator of myeloid progenitor cells, showed the same circadian variation as DNA S-phase (average range of change or ROC = 136%; circadian rhythm: p < 0.001; acrophase of 12:09h). Deoxyribonucleic acid S-phase and CFU-GM in BM both showed a circannual rhythm (p = 0.015 and 0.008) with an identical acrophase of August 12. The daily peak in BM glutathione content, a tripeptide involved in cellular defense against cytotoxic damage, preceded BM proliferative peaks by 4-5 h (ROC = 31-90%; circadian rhythm: p = 0.05; acrophase of 08:30h). Myeloid (ROC = 57%; circadian rhythm: p = 0.056; acrophase at 08:40h) and erythroid (ROC = 26%; circadian rhythm: p = 0.01; acrophase of 13:01h) precursor cells were positively correlated (r = 0.41; p < 0.001), indicating a circadian temporal relationship and equal influence on S-phase of total BM cells. Yield of positive selected CD34+ progenitor stem cells also showed significant circadian variation (ROC = 595%; circadian rhythm: p = 0.02; acrophase of 12:40h). Thus, the temporal synchrony in cell cycling renders BM cells more sensitive at specific times to hematopoietic growth factors and cell cycle-specific cytotoxic drugs. Moreover, proper timing of BM harvesting may improve progenitor cell yield. When using marker rhythms in the blood to allow for individualized timing of BM procedures, the times of low values in white blood corpuscles, neutrophils, and lymphocytes and high values in cortisol were predictive of the times of highest BM erythroid, myeloid, and total S-phase numbers occurring in the following 12 h.     

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.     

Pongamia pinnata influences the circadian variations of liver marker enzymes in hyperammonemic rats

In this study, the influences of Pongamia pinnata, an indigenous medicinal plant used in Ayurvedic and traditional Medicine in India, on the circadian variations of liver marker enzymes in ammonium chloride (AC) induced hyperammonemic rats were studied. Experimental rats (160 - 180 g) were divided into control, AC (daily i.p. injection of AC (100 mg kg^-1 body weight)) treated, AC + P. pinnata ethanolic leaf extract (PPEt) (300 mg kg^-1 body weight) treated and PPEt treated groups. Temporal characteristics (acrophase, amplitude and mesor) of liver marker enzymes; alkaline phosphatase (ALP), aspartate and alanine transaminases (ALT and AST) and γ-glutamyl transferase (GGT) were analyzed. Elevated liver marker enzymes (increased mesor and delayed acrophase of AST, ALT, ALP and GGT) were found in hyperammonemic rats. Administration of PPEt significantly alters these changes. Variations in acrophase, amplitude and r values were also found in control and experimental rats. The detectable circadian rhythms of hepatic marker enzymes and their alterations during AC/PPEt treatments, in the present study, deserve further investigation for the diagnosis and for the therapeutic efficacy of hyperammonemia.     

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.     

Geographical and species variation in circadian rhythm parameters in nemobiine crickets

Abstract. . Locomotor activity rhythms were studied in eight species of nemobiine crickets with different habitat preferences. They showed similar patterns with a major peak of activity around dusk and a minor one around dawn. These patterns did not change within the natural range of daylengm (12–16 h). The acrophase time of the rhythm varied between -3.2 and +3.5 h as measured from dusk, and the free-running period (T) varied between 22.8 and 24.5 h. In the Dianemobius fascipes species complex these circadian parameters varied among nine local strains (8^oS to 43^oN) but did not show any latitudinal trend. In a temperate strain of this species complex (Dianemobius nigrofasciatus from Teshikaga, 43^oN), two lines which differed from each other in mean T by 1.4h were selected, and a high heritability of T, 0.78 + 0.20 (mean±SE) was obtained. On the other hand, in a subtropical strain (Dianemobius fascipes from Ishigaki Island, 24^oN), low heritabilities, 0.35 ± 0.15 for acrophase and 0.17 ± 0.21 for T, were obtained from the full-sib correlations. The variation in i seemed to be random and not related to fitness.     

Intra- and inter-individual variability in the circadian rhythm of body temperature of rats,squirrels, dogs,and horses

In order to explore the often neglected issue of the relationship between intra- and inter-subject variability of circadian rhythms, we evaluated the variability in four parameters of the circadian rhythm of body temperature under controlled laboratory conditions. To avoid the bias of potential selection of an idiosyncratic species, we conducted the study on four different species: the laboratory rat, the thirteen-lined ground squirrel, the domestic dog, and the horse. In rats and squirrels, three of the four parameters of the body temperature rhythm (mean level, amplitude, and regularity of waveform) showed greater inter-subject variability than intra-subject variability. The two variabilities were not different from each other in dogs and horses. Intra- and inter-subject variabilities of acrophase (time of peak) were not significantly different in any of the species, and their magnitudes were similar in all species, which suggests that acrophase is a very dependable parameter in the analysis of circadian rhythms, even though its overall variability is not particularly low.     

Resting breathing frequency in aquatic birds: a comparative analysis with terrestrial species

Several studies have indicated that in birds breathing frequency ( f , breaths min⁻¹) scales to the −1/3 of body weight ( W , kg); this is different from the −1/4 of mammals. We wondered if this discrepancy was due to the peculiar scaling pattern of aquatic birds, as is the case of aquatic mammals. In fact, we had noted previously that the allometric scaling of f differs considerably between aquatic and terrestrial mammals, respectively, W ^−0.42 and W ^−0.25. Measurements of f were obtained in 48 aquatic birds of 22 species and in 35 terrestrial birds of 27 species, during resting conditions on land. Additional data from 11 aquatic and 14 terrestrial species, different from the ones measured, were obtained from the literature. The allometric curve of all species combined (terrestrial and aquatic, n =74) was f =13.3 W ^−0.36, similar to what is reported in previous studies. However, the allometric curve of the aquatic species ( n =33, f =14.5 W ^−0.56) differed greatly ( P <0.001) from that of the terrestrial species ( n =41, f =13.4 W ^−0.26). On average, f of aquatic birds of the 3–5 kg range was 63%, and that of birds of larger size was 57%, of the values of terrestrial birds of similar W . We conclude that, as in mammals, also in terrestrial birds f scales to the −1/4 exponent of W . The similarity of the scaling patterns of f between aquatic birds and mammals suggests a common breathing adaptation to life in the aquatic environment irrespective of phylogenetic relations.     

Biorhythms and pineal gland

Endocrine biorhythms are classified according to the period time, as one of the most characteristic properties of biorhythms. Each endocrine organ has parallel more than one biorhythms with different period time (e. g. circadian and circannual rhythms). The time of acrophase of the biorhythms at the different endocrine organs is fairly variant. This review summarizes the rhythmic function of the THS-thyroid, gonadotrophic-gonadal and ACTH-adrenocortical systems. Pineal gland plays an integrative role in the regulation of rhythmic function of the endocrine system. The melatonin secretion of this gland also reveals conspicuous circadian and circannual rhythms both in mammals and in birds. Mammalian pineal is functional only if its peripheral sympathetic innervation from the superior cervical ganglion is intact. In contrast, melatonin secretion and its circadian rhythm is also maintained in birds under isolated conditions (explanted into an in vitro superfusion system). The 24 hours period time of melatonin circadian rhythm can not be changed by light impulses. The phases of the circadian rhythm, however, can be turned by changing the time of environmental light-dark phases. The wavelength of the artificial light used for reversal of circadian rhythm is an important factor. The development of the entrainment and synchronization of the circadian melatonin rhythm in birds is independent of the rhythmic day-night changes in environmental lighting condition. The differences in the main elements of the biological clock between mammals and birds are discussed.     

Toward a chronophysiology of circulating aldosterone

The physiology of aldosterone secretion has been prominently investigated by homeostatic studies on the levels of the steroid in plasma and/or urine. Aldosterone secretion is, however, arranged in a rhythmic fashion along the 24-hr cycle. The dynamics of aldosterone should thus be reanalyzed chronobiologically in order to gain further insight into the physiology of the hormone. Such a revisitation has been performed in the present study on four groups of clinically healthy volunteers categorized according to sex and age. Aldosterone has been assayed in the plasma of systemic venous blood six times a day (0600, 0800, 1200, 1800, 2000, 0000) in different conditions of physical activity and sodium intake. Time-qualified data have been analyzed by the single-cosinor method and then summarized by the population-mean cosinor procedure to quantify the circadian rhythms in their properties (mesor, amplitude, acrophase). Differences in rhythmometric parameters have been tested by a multivariate analysis for vectorial units. (Hotelling's T2 test). Cosinor analysis indicates that the dynamics of circulating aldosterone substantially changes in relation to posture. The habit of having a routine of diurnal activity leads the circadian rhythm of aldosterone to delay its acrophase from morning to afternoon. The postural shift of acrophase is essentially accompanied by an elevation in the 24-hr mean level. The restriction of salt intake is associated with an increase in mesor; the temporal localization of the circadian crest shows, however, a very high stability. Sex is not characterized by significant differences in the 24-hr patterns of aldosterone in the sense that young males and females show substantially identical time-qualified curves and circadian parameters. Increasing age until the seventh decade in life is responsible for changes mainly in 24-hr mean levels with a slight modification in amplitude. Such a chronophysiology for circulating aldosterone related to the motor-rest schedule, sodium intake, sex, and age, is of interest not only to heuristic but also to practical approaches in clinical medicine.     

Alteration of circadian rhythmicity of CD3+CD4+ lymphocyte subpopulation in healthy aging

The CD4+ T helper/inducer and the CD8+ T suppressor/cytotoxic are major lymphocyte subsets that play a key role in cell-mediated immunity. Aging-related changes of immune function have been demonstrated. The purpose of this study is to analyze the dynamics of variation of these specific lymphocyte subsets in the elderly. In our study cortisol and melatonin serum levels were measured and lymphocyte subpopulation analyses were performed on blood samples collected every four hours for 24 hours from fifteen healthy young middle-aged subjects (age range 36-55 years) and fifteen healthy elderly male subjects (age range 67-79 years). A clear circadian rhythm was validated for the time-qualified changes of CD3+ and CD4+ cells with acrophase at night and for the time-qualified changes of CD8+ cells with acrophase at noon in young middle-aged subjects and for the time-qualified changes of CD3+ cells with acrophase at night and for the time-qualified changes of CD8+ cells with acrophase at noon in elderly subjects. No clear circadian rhythm was validated for the time-qualified changes of CD4+ cells in elderly subjects. No statistically significant correlation among lymphocyte subsets was found in elderly subjects. In elderly subjects CD3+ lymphocyte percentage was higher in the photoperiod and in the scotoperiod and cortisol serum level were higher in the scotoperiod in respect to young middle-aged subjects. In the elderly there is an alteration of circadian rhythmicity of T helper/inducer lymphocytes and this phenomenon might contribute to the aging-related changes of immune responses.     

Predicting the actigraphy-based acrophase using the Morningness–Eveningness Questionnaire (MEQ) in college students of North Italy

Actigraphy is the reference objective method to measure circadian rhythmicity. One simpler subjective approach to assess the circadian typology is the Morningness–Eveningness Questionnaire (MEQ) by Horne and Ostberg. In this study, we compared the MEQ score against the actigraphy-based circadian parameters MESOR, amplitude and acrophase in a sample of 54 students of the University of Milan in Northern Italy. MEQ and the acrophase resulted strongly and inversely associated (r = ?0.84, p < 0.0001), and their relationship exhibited a clear-cut linear trend. We thus used linear regression to develop an equation enabling us to predict the value of the acrophase from the MEQ score. The parameters of the regression model were precisely estimated, with the slope of the regression line being significantly different from 0 (p < 0.0001). The best-fit linear equation was: acrophase (min) = 1238.7–5.49·MEQ, indicating that each additional point in the MEQ score corresponded to a shortening of the acrophase of approximately 5 min. The coefficient of determination, R², was 0.70. The residuals were evenly distributed and did not show any systematic pattern, thus indicating that the linear model yielded a good, balanced prediction of the acrophase throughout the range of the MEQ score. In particular, the model was able to accurately predict the mean values of the acrophase in the three chronotypes (Morning-, Neither-, and Evening-types) in which the study subjects were categorized. Both the confidence and prediction limits associated to the regression line were calculated, thus providing an assessment of the uncertainty associated with the prediction of the model. In particular, the size of the two-sided prediction limits for the acrophase was about ±100 min in the midrange of the MEQ score. Finally, k-fold cross-validation showed that both the model’s predictive ability on new data and the model’s stability to changes in the data set used for parameter estimation were good. In conclusion, the actigraphy-based acrophase can be predicted using the MEQ score in a population of college students of North Italy.     

Differential scaling of the long bones in the terrestrial carnivora and other mammals

We measured the lengths and diameters of four long bones from 118 terrestrial carnivoran species using museum specimens. Though intrafamilial regressions scaled linearly, nearly all intraordinal regressions scaled non-linearly. The observed non-linear scaling of bone dimensions within this order results from a systematic decrease in intrafamilial allometric slope with increasing body size. A change in limb posture (more upright in larger species) to maintain similar peak bone stresses may allow the nearly isometric scaling of skeletal dimensions observed in smaller sized mammals (below about 100 kg). However, strong positive allometry is consistently observed in a number of large terrestrial mammals (the largest Carnivora, the large Bovidae, and the Ceratomorpha). This suggests that the capacity to compensate for size increases through alteration of limb posture is limited in extremely large-sized mammals, such that radical changes in bone shape are required to maintain similar levels of peak bone stress.     

Circadian periodicity of cerebral blood flow revealed by laser-Doppler flowmetry in awake rats: relation to blood pressure and activity

Cardiovascular parameters such as arterial blood pressure (ABP) and heart rate display pronounced circadian variation. The present study was performed to detect whether there is a circadian periodicity in the regulation of cerebral perfusion. Normotensive Sprague-Dawley rats (SDR, approximately 15 wk old) and hypertensive (mREN2)27 transgenic rats (TGR, approximately 12 wk old) were instrumented in the abdominal aorta with a blood pressure sensor coupled to a telemetry system for continuous recording of ABP, heart rate, and locomotor activity. After 5-12 days, a laser-Doppler flow (LDF) probe was attached to the skull by means of a guiding device to measure changes in brain cortical blood flow (CBF). After the animals recovered from anesthesia, measurements were taken for 3-4 days. The time series were analyzed with respect to the midline estimating statistic of rhythm (i.e., mean value of a periodic event after fit to a cosine function), amplitude, and acrophase (i.e., phase angle that corresponds to the peak of a given period) of the 24-h period. The LDF signal displayed a significant circadian rhythm, with the peak occurring at around midnight in SDR and TGR, despite inverse periodicity of ABP in TGR. This finding suggests independence of LDF periodicity from ABP regulation. Furthermore, the acrophase of the LDF was consistently found before the acrophase of the activity. From the present data, it is concluded that there is a circadian periodicity in the regulation of cerebral perfusion that is independent of circadian changes in ABP and probably is also independent of locomotor activity. The presence of a circadian periodicity in CBF may have implications for the occurrence of diurnal alterations in cerebrovascular events in humans.