Circadian changes of heart rate in West syndrome

Patterns of circadian and ultradian rhythms in the heart rate (HR) are described in a full-term baby with birth asphyxia and convulsions. A 24h HR recording was carried out at the age of 1, 15, 56, 289, and 295 days; West syndrome diagnosis was made when the patient was 3 months old. The HR showed no circadian rhythm in the follow-up, whereas it is known that the circadian rhythm appears in healthy infants at the age of 1 month and remains thereafter. This observation may be an indirect indicator of the interference of West syndrome with centers of neurological maturity. (Chronobiology International, 17(4), 591-595, 2000)     

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)     

24-Hour Profiles of Blood Pressure and Heart Rate in Cushing's Syndrome: Relationship Between Cortisol and Cardiovascular Rhythmicities

We monitored the circadian profiles of Cortisol, systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR) in 33 matched normotensive subjects, 32 patients with essential hypertension and 16 patients with Cushing's Syndrome (8 pituitary adenomas, 6 adrenal adenomas and 2 adrenal carcinomas). Each subject underwent serial blood drawings at 4-hr intervals along the 24-hr cycle. BP and HR were automatically recorded every 30 min. Data were analyzed by conventional statistics and by chronobiological procedures (cosinor rhythmometry). Both the control subjects and essential hypertensives showed a circadian profile of BP and HR characterized by a peak in the early afternoon and a clear nocturnal fall (rhythm detection: P< 0.001). The rhythmicity of BP was disrupted in patients affected by Cushing's Syndrome, whereas the 24-hr oscillation of HR was preserved (P < 0.001). Our data are compatible with the view that glucocorticoids are involved in the control of BP circadian rhythm, whereas HR is not under their control.     

Geological cycles

Abstract

Deep body temperature (DBT) and heart rate (HR) circadian rhythms were determined by radiotelemetry in 4 mares kept under controlled light and temperature conditions. Ovulations were determined by rectal palpation of their ovaries. Mean DBT values ranged from 35.85 ± .04 to 37.22 ± .02°C The circadian range of oscillation was extremely low, approximately 0.5° C, with time of maximum temperature occurring midway through the dark period. Mean HR values ranged from 36.4 ± 1.7 to 53.0 ±3.6 beats per min. The circadian range of oscillation was also low, less than 15 beats per min with time of maximum HR occurring approximately at the time of lights off. The HR circacadian rhythm peaked before the DBT circadian rhythm by 3 to 8 hrs. Ovulation did not appear to consistently affect DBT and HR circadian rhythms or their phase relationships.     

Time-Dependent Efficacy of Antihypertensi Agents in Spontaneously Hypertensive Rai

The efficacy of antihypertensive agents was compared when given at different time points in the circadian rhythm. Spontaneously hypertensive rats (SHRs) were kept on a 12/12-h cycle with lights on/off at 07:00/19:00 h. A computerized system was used to measure intraarterial blood pressure and heart rate continuously. Agents or vehicle were intravenously injected at two time points. One at the beginning of the sleeping period, at which low efficacy was expected (T = 10), and one at T = 16, which is 3 h before the circadian peaks in blood pressure (BP) and heart rate (HR), aimed at reducing the rise in BP and HR at awakening. The hypotensive effect of propranolol, metoprolol, labetalol, prazosin, clonidine, and rilmenidine was greater when injected at T = 16 than at T = 10 (p < 0.05 for propranolol, metoprolol, and rilmenidine). In contrast, the renal vasodilators cap-topril and tertatolol were more potent after injection at T = 10. Felodipine was equally effective at both time points. Thus, the effects of antihypertensive agents are related to the phase of the circadian rhythm. The data on the sympatholytic agents in general and β-blockers and centrally acting agents in particular support antihypertensive regimens with timed administrations.     

Chronobiological assessment of habitual physical activity in humans in Western Siberia

The concept of typological variability of physiological individuality was a methodological basis for chrono-physiological assessment of habitual physical activity (HPA) and heart rate (HR) in individuals with different functional types of constitution (FTC) (low HPA (FTC-1), medium HPA (FTC-2), and high HPA (FTC-3)) living at different latitudes of West Siberia (Tyumen, 57°09’N; Khanty–Mansi Autonomous Okrug (KhMAO)–Yugra, 61°00’N; and Yamal–Nenets Autonomous Okrug (YaNAO), 63°12’N). The typical chronostructure of the circadian rhythm of HPA and HR was established for each FTC under the conditions of both mid-latitude (Tyumen) and northern regions. The regional differences were determined too. Compared to the mid-latitude parameters, the chrono-physiological assessment of typological variability of HPA and HR in FTC-1, FTC-2 and FTC-3 subjects living under the climatic and geographical conditions of KhMAO–Yugra and YaNAO in each respective group demonstrated a decrease in the midline-estimating statistic of rhythm (MESOR) and energy intensity of the circadian rhythm, an increase in the proportion of ultradian rhythms, differences in the time of HPA and HR acrophases, a decrease in synchronization and coherence indices, as well as a higher coefficient of the number of heart beats per locomotion and a lower circadian index. All of the above parameters of northerners with each FTC, with regard for the general principles of modern approaches, are not pathologies but rather regional characteristics that should be taken into consideration in the assessment of general state of health and prenosological diagnostics; they were the basis for using chronoprevention and time correction of reduced physical activity.     

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.     

Peripheral clock system circadian abnormalities in Cushing’s disease

ABSTRACT

In Cushing’s syndrome, the cortisol rhythm is impaired and can be associated with the disruption in the rhythmic expression of clock genes. In this study, we evaluated the expression of CLOCK, BMAL1, CRY1, CRY2, PER1, PER2, PER3 genes in peripheral blood leukocytes of healthy individuals (n = 13) and Cushing’s disease (CD) patients (n = 12). Participants underwent salivary cortisol measurement at 0900 h and 2300 h. Peripheral blood samples were obtained at 0900 h, 1300 h, 1700 h, and 2300 h for assessing clock gene expression by qPCR. Gene expression circadian variations were evaluated by the Cosinor method. In healthy controls, a circadian variation in the expression of CLOCK, BMAL1, CRY1, PER2, and PER3 was observed, whereas the expression of PER1 and CRY2 followed no specific pattern. The expression of PER2 and PER3 in healthy leukocytes presented a late afternoon acrophase, similarly to CLOCK, whereas CRY1 showed night acrophase, similarly to BMAL1. In CD patients, the circadian variation in the expression of clock genes was lost, along with the abolition of cortisol circadian rhythm. However, CRY2 exhibited a circadian variation with acrophase during the dark phase in patients. In conclusion, our data suggest that Cushing’s disease, which is characterized by hypercortisolism, is associated with abnormalities in the circadian pattern of clock genes. Higher expression of CRY2 at night outlines its putative role in the cortisol circadian rhythm disruption.     

Pace‐of‐life: Relationships among locomotor activity,life history,and circadian rhythm in the assassin bug,Amphibolus venator

The pace‐of‐life syndrome (POLS) hypothesis means that animal behavior is correlated with life history strategies. Studies have reported that the free‐running period of the circadian rhythm (length of the period) is correlated with life history strategies in some animals. Although the length of the circadian rhythm may be associated with the POLS hypothesis, few studies have investigated the relationships among animal behavior, life history traits, and circadian rhythm. We tested the POLS hypothesis in the assassin bug, Amphibolus venator, which shows individual variation in locomotor activity. We found higher repeatability of differences in locomotor activity between individuals. Moreover, we found a trade‐off between locomotor activity and developmental period such that active individuals developed faster. However, locomotor activity was not correlated with the length of the circadian rhythm in A. venator. Therefore, this study suggests that the length of the circadian rhythm in A. venator does not support the POLS hypothesis.     

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.     

CIRCADIAN PACEMAKER FUNCTION AND ENTRAINMENT DURING MATURATION OF TRANSGENIC HYPERTENSIVE TGR(mREN2)27 AND SPRAGUE-DAWLEY RATS

TGR(mREN2)27 (TGR) transgenic rats develop hypertension due to the mouse mRen-2 gene inserted in their genome. At 5 weeks of age, the blood pressure of TGR rats starts rising, until a maximum is reached at 10 weeks of age. Adult TGR rats show peak values of blood pressure (BP) during the light phase, while heart rate (HR) and motor activity (MA) peak at night. In the present experiment, we evaluated the evolution of circadian rhythms in motor activity, heart rate, and blood pressure of TGR and Sprague-Dawley (SD) rats under 12h light-dark cycles (LD 12:12). Results confirmed that the blood pressure of TGR rats starts to increase at 5 weeks of age, reaching a plateau by the 11th week. Parallel to the increase in blood pressure levels, there was a decrease in the period length of the blood pressure rhythm, a delay in the onset of the alpha phase of the blood pressure rhythm with respect to that of motor activity and heart rate, and a decrease in heart rate levels. In all of the variables studied, the alpha phase of SD rats always started before darkness, whereas that of TGR rats started after lights off. In general, heart rate and motor activity levels of TGR rats were higher than those of SD rats. The amplitude of the circadian rhythms studied was greater in TGR rats than in SD rats. The present results suggest that the different evolution of circadian rhythms in TGR and SD rats might be due to differences in the functioning of the entrainment pathway or the circadian clock itself, which can be detected in young rats and that are probably caused by the expression of the mouse transgene. (Chronobiology International, 18(4), 627–640, 2001)     

Heart rate circadian 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 greater than 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 greater than 63%) with a decrease in amplitude (24%) while in the second group, no circadian rhythm of HR could be detected (RP less than 25%, decrease in amplitude greater than 70%). In the group of patients with a persisting HR 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.     

Circadian rhythm variation in activity, body temperature, and heart rate between C3H/HeJ and C57BL/6J inbred strains.

Inbred mice have been routinely used in studies of genetic effects that determine behavioral variation due to circadian rhythm. In addition to activity patterns (Act), we aimed to characterize variations in the circadian rhythm of deep-body temperature (T(db)) and heart rate (HR) in a specific genetic model of differential cardiorespiratory control. Radiotelemeters were implanted in C3H/HeJ (C3; n = 11) and C57BL/6J (B6; n = 11) inbred strains. Reciprocal first-generation offspring, B6C3F1/J (B6F1; n = 8) and C3B6F1 (C3F1; n = 3) mice, were included to initiate an evaluation of heritable phenotypes. Mice were housed individually in a facility maintained at 23-24 degrees C, and the light-dark cycle was set at 12-h intervals. In each animal, repeated measurements were obtained at 30-min intervals, and the circadian patterns of Act, T(db), and HR were assessed by novel statistical methods that detailed the periodic function for each strain. During the dark phase, B6 mice demonstrated two distinct peaks in Act and T(db) relative to a single early peak for C3 mice. In contrast to the parental strains, B6F1 and C3F1 mice demonstrated intermediate second peaks in Act and T(db). With respect to HR, the C3 strain demonstrated a significantly (P < 0.01) greater daily average compared with B6 mice. The circadian rhythm in HR differed significantly from the Act and T(db) patterns in B6 mice (but not in C3 mice); that is, the periodicity in HR for B6 mice preceded the rise and fall in Act and T(db) during both peaks. The B6 phenotype was also observed in F1 mice. In conclusion, these data suggest that the circadian regulation of Act, T(db), and HR vary significantly among C3, B6, and F1 mice. Furthermore, phenotypic differences between C3 and B6 strains can be used to explore the genetic basis for differential circadian regulation of body temperature and HR.     

Influence of circadian disruption on neurotransmitter levels,physiological indexes,and behaviour in rats

Brain monoamines – such as noradrenaline (NA), dopamine (DA) and serotonin (5-HT) – regulate several important physiological functions, including the circadian rhythm. The purpose of this study was to examine changes in NA, DA and 5-HT levels in various brain regions and their effect on core body temperature (T_c), heart rate (HR) and locomotor activity (Act) in rats following exposure to an artificial light/dark (LD) cycle. For this, male Wistar rats were housed at an ambient temperature (T_a) of 23?°C and 50% relative humidity with free access to food and water. Rats were exposed to either natural (12?h:12?h) or artificial (6?h:6?h) LD cycles for 1 month, after which each brain region was immediately extracted and homogenized to quantify the amounts of NA, DA and 5-HT by high-performance liquid chromatography. Behavioural changes were also monitored by the ambulatory activity test (AAT). Notably, we found that artificial LD cycles disrupted the physiological circadian rhythms of T_c, HR and Act. Although the 5-HT levels of rats with a disrupted circadian rhythm decreased in cell bodies (dorsal and median raphe nuclei) and projection areas (frontal cortex, caudate putamen, preoptic area and suprachiasmatic nucleus) relative to the control group, NA levels increased both in the cell body (locus coeruleus) and projection area (paraventricular hypothalamus). No significant changes were found with respect to DA. Moreover, circadian rhythm-disrupted rats also showed anxious behaviours in AAT. Collectively, the results of this study suggest that the serotonergic and noradrenergic systems, but not the dopaminergic system, are affected by artificial LD cycles in brain regions that control several neural and physiological functions, including the regulation of physiological circadian rhythms, stress responses and behaviour.     

Study of circadian activity in the crayfish <Emphasis Type="Italic">Pontastacus Leptodactylus</Emphasis> during their multimonth maintenance in the river water flow

By the method of non-invasive on-line recording and processing of photoplethysmograms of testaceous invertebrates, the circadian rhythm of cardioactivity was studied in crayfish Pontastacus leptodactylus by recording for several month of the heart rate (HR) and stress-index (characteristics of variational pulsometry). The crayfish were kept in the natural running water in regime of the natural illumination alternation (the first group) or at constant artificial illumination of low intensity (the second group). The circadian rhythm was more frequent and more pronounced in crayfish of the first group. The criteria were established to determine the appearance and stabilization of the nocturnal, active rhythm phase: an increase of HR by more than 30% as compared with the daytime rest period and duration of such increase for at least 2.5 h. The stress-index has been shown to be a reliable parameter of the beginning of the nocturnal phase of cardioactivity, while preservation of the typical circadian rhythm can be considered as a bioindicator in the biomonitoring systems of the quality of surface waters.     

Contribution of the rest–activity circadian rhythm to quality of life in cancer patients

Quality of life (QoL) is estimated from patients scores to items related to everyday life, including rest and activity. The rest–activity rhythm reflects endogenous circadian clock function. The relation between the individual rhythm in activity and QoL was investigated in 200 patients with metastatic colorectal cancer. Patients wore a wrist actigraph (Ambulatory Monitoring Inc., New York, NY) for 3–5 d before chronotherapy, and completed a QoL questionnaire developed by the European Organization for Research and Treatment of Cancer (QLQ-C30) plus the Hospital Anxiety and Depression Scale. The rest–activity circadian rhythm was characterized by the mean activity level (m), autocorrelation coefficient at 24h (r24), and the dichotomy index (I<O), a ratio between the amount of activity while in and out of bed. The distribution of the rest–activity cycle parameters and that of QoL scores was independent of sex, age, primary tumor, number of metastatic sites, and prior treatment. Both the 24h rhythm indicators were positively correlated with global QoL score as well as physical, emotional, and social functioning. Negative correlations were found between m, r24, or I<O and fatigue, appetite loss, and nausea. The rest–activity circadian rhythm appeared to be an objective indicator of physical welfare and QoL. This analysis suggests that circadian function may be one of the biological determinants of QoL in cancer patients.     

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)     

Comparison of circadian rhythm characteristics of blood pressure and heart rate in patients before and after elective coronary artery bypass surgery

Coronary artery bypass grafting surgery (CABGS) is done to reperfuse the ischemic myocardium of coronary disease patients. This study was designed to analyze the circadian rhythm characteristics of blood pressure (BP) and heart rate (HR) of patients before and after CABGS. Fifty-one patients undergoing elective CABGS were studied; 21 patients received one, 12 two and 18 three or more grafts. BP was monitored for 24h before and after CABGS while patients were recumbent in the hospital. Systolic (S) and diastolic (D) BP and HR were assessed every 30 min. Of the 51 patients, 37 (73%) had nondipper 24h BP patterns (nocturnal decline in BP < 10% of daytime mean level) in the preoperative baseline assessment. The peak and MESOR (rhythm-adjusted 24h mean) values of the circadian rhythm in SBP, DBP, and pulse pressure (PP) significantly declined following surgery, while HR and rate-pressure product (RPP = SBP x HR) markedly increased. The double amplitude (peak-to-trough variation) of the circadian rhythm in SBP and DBP was significantly reduced postoperatively, and that of the rhythm in HR and RPP significantly increased. The slopes of the morning rise and evening dip in the 24h SBP profile were reduced significantly after bypass grafting. The corresponding slopes of the HR profile, in contrast, were markedly increased.     

Alterations of the Characteristics of the Circadian Rest‐Activity Rhythm of Cancer In‐Patients

The aim of the present study was to evaluate the characteristics of the circadian rest‐activity rhythm of cancer patients. Thirty‐one in‐patients, consisting of 19 males and 12 females, were randomly selected from the Regional Cancer Center, Pandit Jawaharlal Nehru Medical College, Raipur, India. The rest‐activity rhythm was studied non‐invasively by wrist actigraphy, and compared with 35 age‐matched apparently healthy subjects (22 males and 13 females). All subjects wore an Actiwatch (AW64, Mini Mitter Co. Inc., USA) for at least 4–7 consecutive days. Fifteen‐second epoch length was selected for gathering actigraphy data. In addition, several sleep parameters, such as time in bed, assumed sleep, actual sleep time, actual wake time, sleep efficiency, sleep latency, sleep bouts, wake bouts, and fragmentation index, were also recorded. Data were analyzed using several statistical techniques, such as cosinor rhythmometry, spectral analysis, ANOVA, Duncan's multiple‐range test, and t‐test. Dichotomy index (I<O) and autocorrelation coefficient (r24) were also computed. The results validated a statistically significant circadian rhythm in rest‐activity with a prominent period of 24 h for most cancer patients and control subjects. Results of this study further revealed that cancer patients do experience a drastic alteration in the circadian rest‐activity rhythm parameters. Both the dichotomy index and r24 declined in the group of cancer patients. The occurrence of the peak (acrophase, Ø) of the rest‐activity rhythm was earlier (p<0.001) in cancer patients than age‐ and gender‐matched control subjects. Results of sleep parameters revealed that cancer patients spent longer time in bed, had longer assumed and actual sleep durations, and a greater number of sleep and wake bouts compared to control subjects. Further, nap frequency, total nap duration, average nap, and total nap duration per 1 h awake span were statistically significantly higher in cancer patients than control subjects. In conclusion, the results of the present study document the disruption of the circadian rhythm in rest‐activity of cancer in‐patients, with a dampening of amplitude, lowering of mean level of activity, and phase advancement. These alterations of the circadian rhythm characteristics could be attributed to disease, irrespective of variability due to gender, sites of cancer, and timings of therapies. These results might help in designing patient‐specific chronotherapeutic protocols.     

Simulated microgravity influences circadian rhythm of NIH3T3 cells

Gravity heavily influences living organisms on earth including their circadian rhythm, which is fundamentally important for coordinately physiology in organisms as diverse as cyanobacteria, fungus and humans. Numerous researches have revealed that microgravity in outer space can affect circadian rhythm of astronauts and rodent animals, but the mechanism remains unknown. Using rotary cell culture system to simulate microgravity environment, we investigated the role of simulated microgravity in regulating the circadian rhythm of NIH3T3 cells. Our experiments found that simulated microgravity can not only influence the mRNA level of some core circadian genes, but also modify the circadian rhythm of Per1 and Per2 synchronized after phorbol myristate acetate treatment. Remarkably, MEK/ERK pathway was transiently activated after a 2-h simulated microgravity treatment, with a significant upregulation of Kras, Raf1 and p-ERK1/ERK2. Moreover, U0126, a selective inhibitor of MEK/ERK pathway, could disrupt the circadian rhythm of Per1 and Per2 synchronized after simulated microgravity treatment. Together, our results unveil that simulated microgravity could act like a zeitgeber to influence the circadian rhythm of NIH3T3 by acting on MEK/ERK pathway, indicating that MEK/ERK pathway may act as a bridge which connects cells mechanotransduction pathway and circadian rhythm regulation.