CIRCADIAN PATTERN OF AMBULATORY BLOOD PRESSURE IN UNTREATED HYPERTENSIVE PATIENTS WITH AND WITHOUT METABOLIC SYNDROME

There is a strong association between metabolic syndrome (MS) and increased risk of end-organ damage, cardiovascular disease, stroke, and cardiovascular mortality. Moreover, non-dipping (<?10% decline in the asleep relative to the awake blood pressure [BP] mean) and elevated ambulatory pulse pressure (PP), among other factors related to the circadian BP pattern, have also been associated with increased cardiovascular morbidity and mortality. This cross-sectional study investigated the circadian BP pattern in 2,045 non-diabetic untreated patients with uncomplicated essential hypertension (941 men/1,099 women), 48.7?±?11.9 yrs of age, classified by the presence or absence of MS. BP was measured by ambulatory monitoring for 48 consecutive hours to substantiate reproducibility of the dipping pattern. Physical activity was simultaneously monitored every min by wrist actigraphy to accurately calculate mean BP when awake and asleep for each subject. MS was present in 40.7% of the patients. Patients with MS were characterized by a significantly higher 24?h mean of systolic BP and a lower diastolic BP compared to patients without MS. Accordingly, ambulatory PP was significantly elevated the entire 24?h in MS patients. The prevalence of an altered non-dipper BP profile was significantly higher in MS patients (48.4 vs. 36.1% in patients without MS, p?<?0.001). MS patients were characterized, among other risk factors, by significantly higher uric acid, fibrinogen, leukocyte count, hemoglobin and globular sedimentation velocity, plus lower estimated glomerular filtration rate. Apart from corroborating the significant increased prevalence of a blunted nocturnal BP decline in MS, this study documents ambulatory PP is higher in MS, without differences between groups in mean arterial pressure. This elevated PP might reflect increased arterial stiffness in MS. MS patients were also characterized by elevated values of relevant markers of cardiovascular risk, including fibrinogen and globular sedimentation velocity. These collective findings indicate that MS should be included among the clinical situations in which ambulatory BP monitoring is recommended. (Author correspondence: rhermida@uvigo.es)     

Rhythmic egg-laying behaviour in virgin females of fruit flies Drosophila melanogaster

Fruit fly Drosophila melanogaster females display rhythmic egg-laying under 12:12?h light/dark (LD) cycles which persists with near 24?h periodicity under constant darkness (DD). We have shown previously that persistence of this rhythm does not require the neurons expressing pigment dispersing factor (PDF), thought to be the canonical circadian pacemakers, and proposed that it could be controlled by peripheral clocks or regulated/triggered by the act of mating. We assayed egg-laying behaviour of wild-type Canton S (CS) females under LD, DD and constant light (LL) conditions in three different physiological states; as virgins, as females allowed to mate with males for 1?day and as females allowed to mate for the entire duration of the assay. Here, we report the presence of a circadian rhythm in egg-laying in virgin D. melanogaster females. We also found that egg-laying behaviour of 70 and 90% females from all the three male presence/absence protocols follows circadian rhythmicity under DD and LL, with periods ranging between 18 and 30?h. The egg-laying rhythm of all virgin females synchronized to LD cycles with a peak occurring soon after lights-off. The rhythm in virgins was remarkably robust with maximum number of eggs deposited immediately after lights-off in contrast to mated females which show higher egg-laying during the day. These results suggest that the egg-laying rhythm of D. melanogaster is endogenously driven and is neither regulated nor triggered by the act of mating; instead, the presence of males results in reduction in entrainment to LD cycles.     

FAILURE OF EXTRAOCULAR LIGHT TO FACILITATE CIRCADIAN RHYTHM REENTRAINMENT IN HUMANS

Although extraocular light can entrain the circadian rhythms of invertebrates and nonmammalian vertebrates, almost all studies show that the mammalian circadian system can only be affected by light to the eyes. The exception is a recent study by Campbell and Murphy that reported phase shifts in humans to bright light applied with fiber-optic pads behind the knees (popliteal region). We tested whether this extraocular light stimulus could accelerate the entrainment of circadian rhythms to a shift of the sleep schedule, as occurs in shift work or jet lag. In experiment 1, the sleep/dark episodes were delayed 8h from baseline for 2 days, and 3h light exposures were timed to occur before the temperature minimum to help delay circadian rhythms. There were three groups: (1) bright (about 13,000 lux) extraocular light from fiber-optic pads, (2) control (dim light, 10–20 lux), and (3) medium-intensity (about 1000 lux) ocular light from light boxes. In experiment 2, the sleep/dark episodes were inverted, and extraocular light was applied either before the temperature minimum to help delay circadian rhythms or after the temperature minimum to help advance rhythms. Circadian phase markers were the salivary dim light melatonin onset (DLMO) and the rectal temperature minimum. There was no evidence that the popliteal extraocular light had a phase-shifting effect in either experiment. Possible reasons for phase shifts in the Campbell and Murphy study and not the current study include the many differences between the protocols. In the current study, there was substantial sleep deprivation before the extraocular light was applied. There was a large shift in the sleep/dark schedule, rather than allowing subjects to sleep each day from midnight to noon, as in the Campbell and Murphy study. Also, when extraocular light was applied in the current protocol, subjects did not experience a change from sleeping to awake, a change in posture (from lying in bed to sitting in a chair), or a change in ocular light (from dark to dim light). Further research is necessary to determine the conditions under which extraocular light might produce phase shifts in human circadian rhythms. (Chronobiology International, 17(6), 807–826, 2000).     

The Variability in Circadian Phase and Amplitude Estimates Derived from Sequential Constant Routines

Both the constant routine (CR) and the dim light melatonin onset have been suggested as reliable methods to determine circadian phase from a single circadian cycle. However, both techniques lack published studies quantifying the intercycle variability in their phase resolution. To address this question eight healthy male subjects participated in two CRs, 7 days apart. Circadian phase was determined using 3-min samples of core body temperature and two hourly urinary sulphatoxy melatonin excretion rates. Phase and amplitude were estimated using simple (24 h) and complex (24 + 12 h) cosinor models of temperature data and the onset, offset, and a distance-weighted-least-squares (DWLS) fitted acrophase for the melatonin metabolite. The variability in phase estimates was measured using the mean absolute difference between successive CRs. Using the simple 24 h model of temperature data, the mean absolute phase difference was 51 min (SD = 35 min). Using the complex model, the mean absolute phase difference was 62 min (SD = 35 min). Using the DWLS fitted acrophase for the melatonin metabolite, the mean absolute phase difference between CR1 and CR2 was 40 min (SD = 26 min). The results indicate that for CRs a week apart, the mean absolute difference in an individual's phase estimate can vary by 40-60 min depending on the choice of dependent measure and analytic technique. In contrast to the intraindi-vidual variability, the group results showed considerably less variability. The mean algebraic difference between CRs, using temperature- or melatonin-derived estimates, was less than 5 min, and well within the range of normal measurement error.     

Biological Time‐Dependent Difference in Effect of Peroxynitrite Demonstrated by the Mouse Hot Plate Pain Model

We previously demonstrated the rhythmic pattern of L‐arginine/nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) cascade in nociceptive processes. The coupled production of excess NO and superoxide leads to the formation of an unstable intermediate peroxynitrite, which is primarily responsible for NO‐mediated toxicity. In the present study, we evaluated the biological time‐dependent effects of exogenously administered peroxynitrite on nociceptive processes and peroxynitrite‐induced changes in the analgesic effect of morphine using the mouse hot‐plate pain model. Experiments were performed at four different times of day (1, 7, 13, and 19 hours after lights on, i.e., HALO) in mice of both sexes synchronized to a 12 h:12 h light‐dark cycle. Animals were injected intraperitoneally (i.p.) with saline or 10 mg/kg morphine 30 min before and 0.001 mg/kg peroxynitrite 30 sec before hot‐plate testing, respectively. The analgesic effect of morphine exhibited significant biological time‐dependent differences in the thermally‐induced algesia; whereas, administration of peroxynitrite alone exhibited either significant algesic or analgesic effect, depending on the circadian time of its injection. Concomitant administration of peroxynitrite and morphine reduced morphine‐induced analgesia at three of the four different study time points. In conclusion, peroxynitrite displayed nociceptive and antinociceptive when administered alone according to the circadian time of treatment, while it diminished analgesic activity when administered in combination with morphine at certain biological times.     

Age-Related Differences of Blood Pressure Profile in Essential Hypertension

The purpose was to assess age-related circadian changes of blood pressure profile (BPP) employing a truncated Fourier series with four harmonics (tFs) in patients with essential hypertension. The study was performed on 32 patients with essential hypertension divided in two groups: (A) 15 patients younger than 55 years and (B) 17 patients older than 60 years. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were monitored every 20 minutes for 24h with a noninvasive portable device (SpaceLabs 90202). To evaluate the existence of SBP and DBP circadian rhythms a one-sample runs-test was performed and the mesor, amplitude, and acrophase from the overall curve of each patient were obtained by tFs. In both groups, SBP and DBP profiles showed a first peak in the late morning and a second peak in the early evening around the same hours. The two peaks in the SBP profile were higher and the two peaks in the DBP profile were lower in older patients than in younger ones (p. 01, p <. 05, p>. 3, p>. 05). The truncated Fourier series with four harmonics evidences different age-related BP profiles characterized by two peaks with higher SBP and lower DBP in elderly patients. These changes of BPP are in accordance with the reported higher risk of cardiovascular events observed around the same hours. (Chronobiology International, 14(4), 397–407, 1997)     

Circadian Rhythm of Blood Pressure and Heart Rate in Healthy Persons and Kidney Transplant Patients: Correlations with Activity

Fourteen diurnally active (07: 00–22: 39 h) normotensive healthy control subjects and 14 kidney transplant patients were studied by ambulatory blood pressure monitoring and wrist actigraphy simultaneously during one 24-h period. In the control group, circadian rhythms in systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressure, heart rate (HR), and wrist activity were documented by cosinor analysis with comparable afternoon peak times. In contrast, circadian rhythms with afternoon acrophases were detected only in HR and wrist activity in the patient group. The correlation of wrist activity with HR in controls and patients was comparable. Wrist activity and blood pressure were associated (r = 0.65 DBP and 0.54 SBP; p < 0.05) in controls, while in patients the relationship was weak or absent (r ranging from 0.02 SBP to 0.22 DBP). In 6 of 14 patients, BP and wrist activity were negatively correlated, reflecting the existence of nocturnal hypertension. In eight others, the correlation was small but positive. The 24-h pattern in BP and wrist activity in controls was comparably phased; however, this was not the case for the transplant patients, indicating the day-night pattern in blood pressure in this group is strongly dependent on pathologic phenomena rather than activity level and pattern.     

Physical activity,and not fat mass is a primary predictor of circadian parameters in young men

Circadian rhythms are ≈24?h oscillations in physiology and behavior, and disruptions have been shown to have negative effects on health. Wrist skin temperature has been used by several groups as a valid method of assessing circadian rhythms in humans. We tested the hypothesis that circadian temperature amplitude (TempAmp) and stability (TempStab) would significantly differ among groups of healthy young men of varying adiposities, and that we could identify physiological and behavioral measures that were significantly associated with these temperature parameters. Wrist skin temperatures taken at 10?min intervals for 7 consecutive days were determined in 18 optimal (OGroup), 20 fair (FGroup) and 21 poor (PGroup) %Fat grouped young men and subsequently analyzed using available validated software. Body composition, cardiorespiratory fitness, actigraphy, daily nutritional and sleep data, and fasting lipid, insulin and glucose concentration measures were also determined. Significant changes in TempAmp and TempStab parameters in subjects with a single metabolic syndrome (MetS) risk factor compared to those with no MetS factors was observed. In addition, stepwise multivariate regression analyses showed that 50% of the variance in TempAmp was explained by actigraphy (mean steps taken per day; MSTPD), cardiorespiratory fitness, and late night eating per week (#LNE); and 57% in TempStab by MSTPD, time spent in moderate-to-vigorous activity per day, fat mass, and #LNE. Overwhelmingly, physical activity was the most important measure associated with the differences in circadian rhythm parameters. Further research is warranted to determine the effects of increasing the amount and timing of physical activity on the status of the circadian system in a variety of populations.     

In Sync with the Family: Children and Partners Influence the Sleep‐Wake Circadian Rhythm and Social Habits of Women

Different factors have been proposed to influence morningness‐eveningness, biological rhythms, and sleep‐wake cycles, but few studies focused on the influence of social habits. Here, we focus on the influence of children and partners on the social habits of women at different stages of their lives and on synchronization within the family. One hundred and seventy‐nine women participated in the study and were allocated into four groups: women without children, pregnant women without children, pregnant women with children, and non‐pregnant mothers. Morningness was predicted by the presence of children, and earlier chronotype was predicted by the presence of children, pregnancy, and age. Average sleep duration was longest in pregnant women. The presence of children was responsible for a difference in rise times of approximately 1.5 h on the weekend. Subjective sleep‐onset latencies were shortest in women with children. The synchrony between partners (husband/wife) was 0.46 in women without children, 0.79 in pregnant women, 0.40 in women with children, and 0.56 between mother and child. Partners’ chronotypes were highly correlated, as were those of mother and child. This study suggests children have a strong influence on their mother's lifestyle and sleep‐wake rhythm, far beyond the first months of life, and that children are a more important social factor than the male partner.