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The long-term effects of phase advance shifts of photoperiod on cardiovascular parameters
as measured by radiotelemetry in rats
View the table of contents for this issue, or go to the journal homepage for more
2013 Physiol. Meas. 34 1623
(http://iopscience.iop.org/0967-3334/34/12/1623)
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IOP PUBLISHING PHYSIOLOGICAL MEASUREMENT
Physiol. Meas. 34 (2013) 1623–1632 doi:10.1088/0967-3334/34/12/1623
The long-term effects of phase advance shifts of
photoperiod on cardiovascular parameters as
measured by radiotelemetry in rats
L Molcan1, M Teplan2,AVesela
1and M Zeman1
1Department of Animal Physiology and Ethology, Faculty of Natural Sciences,
Comenius University, Bratislava, Slovak Republic
2Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovak Republic
E-mail: mzeman@fns.uniba.sk
Received 30 August 2012, accepted for publication 9 January 2013
Published 28 October 2013
Online at stacks.iop.org/PM/34/1623
Abstract
Cardiovascular parameters, such as blood pressure and heart rate, exhibit
both circadian and ultradian rhythms which are important for the adequate
functioning of the system. For a better understanding of possible negative effects
of chronodisruption on the cardiovascular system we studied circadian and
ultradian rhythms of blood pressure and heart rate in rats exposed to repeated
8 h phase advance shifts of photoperiod. The experiment lasted 12 weeks,
with three shifts per week. Spectral power as a function of frequency for both
circadian and harmonic ultradian rhythms was expressed as the circadian–
ultradian power ratio. The circadian rhythms of blood pressure, heart rate and
locomotor activity were recorded during the control light:dark (LD) regimen
with higher values during the D in comparison with the L. Phase advance shifts
resulted in a diminished circadian–ultradian power ratio for blood pressure,
heart rate and locomotor activity indicating suppressed circadian control of
these traits greater in heart rate than blood pressure. In conclusion, rats kept
under irregular LD conditions have suppressed circadian control of heart rate,
blood pressure and locomotor activity and rely more on an acute response to
the LD regime. Their ability to anticipate regular loads can be weakened and in
this way chronodisruption can contribute to the pathogenesis of cardiovascular
diseases.
Keywords: radiotelemetry, circadian rhythm, ultradian rhythm, blood pressure,
heart rate
0967-3334/13/121623+10$33.00 © 2013 Institute of Physics and Engineering in Medicine Printed in the UK & the USA 1623
1624 L Molcan et al
1. Introduction
Biological clocks have developed in organisms exposed to regular changes of environment,
mainly a light:dark (LD) cycle. These clocks generate circadian rhythms that are endogenous
with a period close to 24 h and help organisms anticipate regular changes of environmental
conditions. In contrast to circadian rhythms, ultradian rhythms are biological oscillations with
a period shorter than 20 h. Ultradian and circadian rhythms form a temporal organization
of organisms and have a generally accepted role in the control of the cardiovascular system
(Durgan and Young 2010). As such, the cardiovascular system exhibits distinct circadian and
ultradian rhythms in its parameters, amongst which blood pressure (BP) and heart rate (HR)
have been most studied (Yates and Benton 1991).
Circadian rhythms are governed by the master clock localized in the suprachiasmatic
nuclei of the hypothalamus. Deletion of the suprachiasmatic nuclei results in a loss of the
circadian pattern of BP, HR and locomotor activity (Witte et al 1998). Further evidence for
the link between suprachiasmatic nuclei and BP circadian rhythmicity comes from recent
studies with transgenic mice that lack the functional expression of a vasoactive intestinal
polypeptide receptor gene (Vipr 2-/-). These studies show significant residual rhythms of
BP in control mice that were not found in a Vip r 2-/- mutant strain (Sheward et al 2010).
Moreover, spontaneously hypertensive rats, that are used as a model of essential hypertension,
have a shorter endogenous circadian period of wheel running (Peters et al 1994) and different
responses to phase shifts of the LD cycle in comparison with normotensive rats (Avidor et al
1989). Also, the transplantation of the rostral hypothalamus containing the suprachiasmatic
nuclei from spontaneously hypertensive rats to normotensive rats resulted in the increase of
BP (Eilam et al 1991). Finally, in transgenic rats with additional copies of the renin gene,
circadian rhythms of BP are out of phase with the physical activity indicating that locomotor
activity itself cannot explain the daily variations in BP (Lemmer et al 1993). Therefore, when
taken as a whole, the current research does indicate a role of the suprachiasmatic nuclei in
control of BP rhythm.
BP is controlled via baro-, chemo- and osmo-receptors together with hormones which
exhibit ultradian rhythmicity. For example, 8 h oscillations have been recorded for endothelin-
1levels(Heroldet al 1998) along with 60–150 min oscillations for insulin (Lefcourt et al
1999), approximately 60 min pulses of glucocorticoids (Conway-Campbell et al 2012) and
50–100 min for epinephrine and 12 h oscillations for norepinephrine (Schoefl et al 1997).
The direct interactions between circadian and ultradian rhythms in BP control are not
well understood. However, some understanding may come from the fact that spontaneously
hypertensive rats have been found to have significantly more ultradian than circadian power
in comparison with normotensive rats. It is therefore assumed that the circadian rhythm
may modulate the power in the ultradian band and this modulation is more pronounced in
normotensive rats amongst which ultradian activity is higher during the active phase of the day,
than in spontaneously hypertensive rats (Holstein-Rathlou et al 1995). The circadian but not
ultradian rhythmicity of BP is controlled by vascular autonomic activity (Oosting et al 1997)
and the increased BP variability in the ultradian frequency range cannot just be a consequence
of the increased BP per se (Holstein-Rathlou et al 1995).
HR is another important cardiovascular trait controlled mainly via the autonomous
nervous system that exhibits a strong circadian and ultradian pattern. Experimental studies
with suprachiasmatic nucleus lesioned normotensive rats provide clear evidence that the
suprachiasmatic nucleus is one of the key intrinsic factors contributing to the control of
circadian fluctuations in HR (Warren et al 1994). Cardiac function is characterized by irregular
time intervals between consecutive heart beats (Acharya et al 2006). The sinoatrial node acts
Cardiovascular rhythms in rats exposed to phase advance shifts 1625
as the primary pulse generator for heart beats. Other sympathetic and parasympathetic neurons
and local circuits of the intrinsic cardiac nervous system, as well as the artrioventricular node,
temperature changes and endocrine influences are also capable of modulating autonomous
heart beat stimulation properties (Hu et al 2008). In terms of ultradian rhythms of HR
both plasma catecholamines and intrinsic myocardial activity are potential sources of control
(Koch et al 1999). Furthermore, correlations across a range of time scale invariant periods
(from minutes to 24 h) suggest that the mechanisms related to suprachiasmatic nuclei and
peripheral cardiac regulations are coupled (Hu et al 2008).
Alterations in the cardiac scale invariance are associated with cardiovascular diseases and
predict reduced survival rates (Bigger et al 1996, Makikallio et al 2004). As such, shift work
that results in the disruption of circadian organization can be involved in lifestyle disease
development or progression (Boggild and Knutsson 1999). However, epidemiological studies
have not provided unequivocal results till now mainly due to methodological limitations in
many of these studies (Wang et al 2011). Therefore, more focused experimental studies are
needed to understand the mechanisms that induce chronodisruption and its possible negative
effects on the cardiovascular system.
The purpose of our experiment was to investigate changes in cardiovascular parameters
after repeated LD shifts under controlled laboratory conditions in rats. We evaluated circadian
and ultradian rhythms of BP and HR under synchronized and unsteady LD conditions to reveal
if repeated phase advance shifts (PAS) of the LD cycle were able to change absolute levels
of BP and HR. Moreover, we aimed to characterize the relationships between ultradian and
circadian rhythms under regular and irregular lighting cycles.
2. Materials and methods
2.1. Animals
Normotensive mature male Wistar rats (n=8; 356 ±8 g) were kept under controlled
temperature, 21 ±1◦C, conditions under a regular 12L:12D cycle, with lights on from
06:00. Light intensity was 150 lux as measured with an automatic datalogger (KIMO KH100,
Chevrier Instruments Inc., Canada). The rats were housed singly with food and water ad
libitum. The experiment was approved by the Ethical Committee for the Care and Use of
Laboratory Animals at the Comenius University in Bratislava, Slovak Republic, and the State
Veterinary Authority.
2.2. Measurement of cardiovascular parameters and the experimental design
The cardiovascular parameters were measured with a radiotelemetry device (Data Science
International, St Paul, Minnesota, USA) that allows continuous measurement of BP, HR and
locomotor activity in freely moving animals. The implementation procedure for the device is
as previously validated at our department (Molcan et al 2009) and is as follows. Before the
surgery the rats were anesthetized by a ketamine hydrochloride (75 mg kg−1) and xylazine
hydrochloride (10 mg kg−1) mixture. The pressure radiotelemetric transmitter TA11PA-C40
(DSI, USA) was surgically implanted into the abdominal aorta just above its bifurcation
(Brockway et al 1991). The catheter was then stabilized to the aorta with tissue glue (3M
Vetbond; DSI, USA) and a cellulose patch (Cellulose Patch Kit—Small Animals; DSI, USA).
The transmitter battery was then secured to the muscular wall.
1626 L Molcan et al
Figure 1. The experimental design consisted of 1 week of 12 h light (L) and 12 h dark (D) and then
12 weeks of PAS. Longer horizontal black bars represent the dark phase (4 or 12 h) of the day.
2.3. Experimental protocol
The animals were included into the experiment 2 weeks after the surgical procedure. Data
were acquired by scheduled sampling interval of 10 s with segment duration of 30 s for BP,
HR and locomotor activity. At first, the rats were kept for 1 week under control LD conditions.
Afterwards, they were exposed for 12 weeks to 8 h PAS three times per week. Radiotelemetric
sensors were ON during weeks 1, 5, 10 and 11 of the experiment when the PAS were applied
(figure 1).
2.4. Time series analysis and statistical evaluation
We evaluated HR, mean BP (mean arterial pressure (MAP)) and locomotor activity from the
acquired data. The paired t-test and repeated measures ANOVA with the Fisher LSD post-hoc
test were used for the evaluation of differences between groups. Values are presented as mean
±the standard error of the mean (s.e.m.). Circadian and ultradian rhythm analysis of the
individual measured data was performed with a Lomb–Scargle periodogram using Chronos-
Fit software (Zuther et al 2009). The circadian to ultradian power rhythm ratio (CUPR)
was calculated from the original filtered data as a ratio of circadian (24 h) and the average of
ultradian (12, 8, 6, 4.8 and 4 h) periods. Since the Shapiro–Wilk normality test of power spectra
rejected the null hypothesis for a normal data distribution, the non-parametric Friedman test
followed by the Wilcoxon test for multiple comparisons was used. Due to catheter closing in
two rats during the experiment, six animals were used for evaluation of long-term differences
among weeks while the evaluation of LD differences during the control lighting regimen was
performed with eight rats.
3. Results
Rats exposed to control LD conditions exhibited distinct circadian rhythms in HR, with higher
values during the active (D) in comparison with the passive (L) phase of the day (L: 315 ±6
beats min–1;D:355 ±8 beats min–1;t=11.658; n=8; p<0.001). Similarly, both MAP (L:
96 ±2 mm Hg; D: 100 ±2mmHg;t=5.852; n=8; p<0.01) and locomotor activity (L:
0.9 ±0.1 counts min–1;D:3 ±0.4 counts min–1;t=6.094; n=8; p<0.001) reached higher
levels during the dark phase than during the light phase. Significant dominance of circadian
rhythm power over harmonic ultradian rhythm power was calculated for the entrained rhythms
Cardiovascular rhythms in rats exposed to phase advance shifts 1627
(A) (B) (C)
(D) (E) (F)
Figure 2. The rats exposed to 12 weeks of PAS revealed a decreasing profile of 24 h (circadian)
periods for HR (A), MAP (B) and locomotor activity (C) while average harmonic ultradian (12, 8, 6,
4.8 and 4 h) periods for HR (D), MAP (E) and locomotor activity (F) did not alter. Yaxis—spectral
power calculated by a Lomb–Scargle periodogram. Columns with different superscript letters are
statistically different. Error bars indicate s.e.m.
Tab l e 1 . Average daily values of HR, MAP and locomotor activity (LA) ±s.e.m. of rats (n=6)
exposed at first to control 12 h light and 12 h dark conditions and then 8 h PAS of light (weeks 01,
05, 10 and 11—S01, S05, S10 and S11, respectively). L and D differences are expressed as D–L
values. Statistical significance (∗∗ p<0.01; ∗∗∗ p<0.001) is expressed in comparison to the LD
week.
HR (beats min–1) MAP (mm Hg) LA (counts min–1)
Mean D −L Mean D −L Mean D −L
LD 337 ±837±4 99.2 ±1.1 2.7 ±1.0 1.8 ±0.4 1.8 ±0.4
S01 345 ±5∗∗∗ 20 ±2∗∗∗ 100.3 ±0.9 1.7 ±0.3 2.0 ±0.3 1.1 ±0.3
S05 333 ±621±2∗∗∗ 99.8 ±0.7 1.9 ±0.5 1.8 ±0.2 0.6 ±0.2∗∗
S10 303 ±7∗∗∗ 19 ±2∗∗∗ 96.3 ±0.7∗∗∗ 1.2 ±0.5 1.9 ±0.2 0.4 ±0.2∗∗∗
S11 307 ±8∗∗∗ 23 ±4∗∗ 98.6 ±0.7 1.8 ±0.5 1.8 ±0.2 0.7 ±0.2∗∗
of HR (t=6.704; n=8; p<0.001), MAP (t=3.573; n=7; p<0.05) and locomotor activity
(t=5.951; n=8; p<0.001) under the LD 12:12 regimen (figure 2).
The repeated exposure of rats to PAS decreased mean HR (F(4,40) =81.796; p<0.001)
as well as resulted in differences between L and D values (table 1). During the first week of
PAS we found negative D −L values after three shift days while on week 10 or 11 a positive
D−L ratio was calculated for all measured parameters (figure 3). 11 weeks of PAS exposure
failed to affect MAP values as compared to the BP measured in rats kept under control LD
conditions (LD: 99.2 ±1.1 mm Hg versus PAS week 11: 98.6 ±0.7 mm Hg).
1628 L Molcan et al
(A)
(B)
(C)
(D)
(E)
(F)
Figure 3. The daily (A), (B), (C) and weekly (D), (E), (F) pattern of HR (A), (D), mean arterial
BP (B), (E) and locomotor activity (C), (F) in rats (n=6) exposed for 1 week to control 12L:12D
conditions and for 12 weeks (S01, S05, S10, S11) to PAS three times per week. The dark solid
lines (A), (B), (C) and dark bars (D), (E), (F) represent the dark phase mean values and the dotted
lines (A), (B), (C) and gray bars (D), (E), (F) represent the light phase mean values. Columns with
superscripts are statistically different. Error bars indicate s.e.m.
The spectral power of circadian rhythms in HR decreased markedly during the first 5 weeks
of PAS exposure (figure 2(A)) in comparison with the initial LD values (p<0.05). The decrease
of spectral power of circadian rhythms for locomotor activity (p<0.01; figure 2(C)) paralleled
the pattern in HR. The decline in MAP was less pronounced and diminished values (p<0.05)
were recorded for week 10 in comparison with the first week (figure 2(B)). The circadian to
ultradian spectral power ratio for HR decreased to a half after the first week and to a quarter
of initial power values during week 11 of PAS exposure (figure 4). This decline of CUPR
reflects diminished circadian variability in spectral power while ultradian spectral power was
not changed (figures 2(D), (E), (F)). CUPR for MAP (p=0.11) and locomotor activity (p<
0.05) exhibited a similar declining pattern as for HR (p<0.01) after PAS exposure but the
decrease was less pronounced. The Wilcoxon multiple comparison test of CUPR for MAP
revealed a significant (p<0.05) decrease in comparison to LD values only in week 5 of PAS
exposure. Finally, CUPR for locomotor activity decreased significantly (p<0.05) for weeks
5 and 10 in comparison with the first PAS week values (figure 4).
4. Discussion
Rats exposed to regular 12L:12D conditions exhibited the expected differences in HR, MAP
and locomotor activity between the active (D) and passive (L) phases of the daily cycle, with
higher values occurring during the D in comparison to the L phase. This finding is in accordance
Cardiovascular rhythms in rats exposed to phase advance shifts 1629
Figure 4. The circadian to ultradian power ratio changed with time for HR (black), less for mean
arterial BP (gray) and locomotor activity (white). The data are expressed as mean ±s.e.m.;
LD—control LD week; S01, S05, S10 and S11—weeks 1, 5, 10 and 11 of PAS, respectively;
Yaxis—ratio of circadian (24 h) to ultradian harmonic (12, 8, 6, 4.8 and 4 h) period power.
Columns with different superscript letters are statistically different. Error bars indicate s.e.m.
with previously published data (Witte et al 1998). The experimental design involving repeated
8 h PAS three times per week, which lasted for 12 weeks, resulted in a decrease of HR but
no significant changes of MAP and locomotor activity values. Similar decreases in HR have
also been previously observed in rats exposed to photoperiod manipulation by advancing the
dark phase by4horbyadvancing and delaying the dark phase by2h(Zhang et al 2000). The
decrease of HR may result either from increased parasympathetic tone activity or decreased
sympathetic tone activity induced by the photoperiod changes. Different patterns of HR and
locomotor activity over the 12 week period clearly show that the locomotor activity profile
cannot explain the observed alterations in hemodynamic variables.
The expected circadian rhythms of measured variables were observed in rats exposed to
control lighting cycles. Specifically, the highest circadian power was shown for HR, which
was more than 20 times higher in comparison with the power of harmonic ultradian rhythms.
Approximately eight times higher power of circadian over ultradian period has been shown
for MAP and locomotor activity. These results are in line with data obtained in rats exposed
to a normal LD cycle (Witte and Lemmer 1995).
The circadian power of HR, MAP and locomotor activity was diminished after PAS
exposure. The circadian pattern was well detectable for HR, MAP and locomotor activity
during the first week of PAS. During the next weeks of PAS exposure (weeks 5, 10 and 11),
CUPR decreased. Daily changes of MAP represent an output of several control centres and,
at least in humans, ultradian rhythms oscillate independently from 24 h rhythm parameters
(Kawamura et al 2003, Hadtstein et al 2004). Therefore, the generation and regulation of
ultradian rhythms must be able to be influenced independently of the circadian rhythm control
centre (Perez-Lloret et al 2004). For example, suprachiasmatic nucleus lesions of rats kept
under 12L:12D resulted in only an incomplete abolishing of day–night variations (Witte et al
1998) and rats after ablation of suprachiasmatic nuclei were still able to discriminate between
a morning and an afternoon feeding session (Mistlberger et al 1996).
A complex interaction model (neuronal, endocrine, excretion) is involved in the control of
circadian and ultradian rhythms in BP. However, the ultradian changes in the functions of the
autonomic nervous system have been assumed to be responsible for the ultradian oscillations
of BP (Benton and Yates 1989). Since higher BP or non-dipping status leads to target-organ
damage (Syrseloudis et al 2011), good control of BP is important in order to keep BP in a
distinct range over a day. Therefore, stable and multilevel regulations are necessary for BP
control while a rapid and relatively simple control system is needed for HR control.
1630 L Molcan et al
HR is controlled mainly via sinoatrial node pacemaker cells and autonomous nervous
system branches (Mighiu and Heximer 2012) which are modulated directly by the
suprachiasmatic nuclei (Buijs et al 2003, Scheer et al 2003). The circadian pattern of HR has
been shown to be completely abolished in rats with suprachiasmatic nuclei ablation (Warren et
al 1994, Sheward et al 2010). Moreover, the suprachiasmatic nucleus itself contains interacting
nodes that together with the intrinsic cardiac nodes are responsible for scale invariance of HR
fluctuations (Hu et al 2008).
In our experiment, rats entrained to LD exhibited a pronounced 24 h pattern, more so
for HR than for MAP. Since the number of factors and the resulting interactions involved in
the generation of circadian and ultradian rhythms of BP are higher than those for HR, (1)
exposure to LD conditions resulted in smaller CUPR for MAP than for HR and (2) long-term
PAS exposure induced a smaller decrease in CUPR for MAP as compared with CUPR for HR.
However, our experimental design did not allow us to differentiate whether the rhythmicity in
cardiovascular parameters was due to periodic masking effects or truly reflected the activity
of the endogenous pacemaker.
We assume that the irregular LD conditions disturbed circadian outputs from the
suprachiasmatic nuclei which influenced the circadian rhythmicity of HR, MAP and locomotor
activity. Our results demonstrate that circadian rhythms in HR are more sensitive to
disturbances caused by PAS than BP. Since both ultradian and circadian rhythms can help
the cardiovascular system to adapt to changing environmental conditions, disturbed daily
variability of cardiovascular parameters could be involved in an inadequate response to stress
conditions. Under unpredictable conditions the abilities of organisms to predict environmental
changes can decrease and the loss of predictability may result in higher stress responses to
unexpected negative aspects of the environment. This has implications for those individuals
who are exposed to shift work, especially in unpredictable high stress environments such as
hospitals or industrial settings.
5. Conclusions
In conclusion, in mature male Wistar rats exposed to the long-term PAS, BP did not change and
HR values decreased over a 12 week experimental period. In addition, a prominent circadian
variability of HR, MAP and locomotor activity was shown under LD cycles. Furthermore,
long-time exposure to PAS resulted in a decrease of circadian rhythm dominance more for
HR than BP and no alterations of ultradian rhythms. As such, disrupted circadian control of
the cardiovascular system may disturb the anticipation of regular loads and contribute to the
pathogenesis of cardiovascular diseases.
Acknowledgments
This research was supported by APVV-0214-07, APVV-0150-10, VEGA 2/0043/13 and
NOREG grants. The authors also thank Ben Lewis Evans for his comments on the manuscript
and English editing.
References
Acharya U R, Joseph K P, Kannathal N, Lim C M and Suri J S 2006 Heart rate variability: a review Med. Biol. Eng.
Comput. 44 1031–51
Avidor R, Eilam R, Malach R and Gozes I 1989 VIP-mRNA is increased in hypertensive rats Brain Res. 503 304–7
Cardiovascular rhythms in rats exposed to phase advance shifts 1631
Benton L A and Yates F E 1990 Ultradian adrenocortical and circulatory oscillations in conscious dogs Am. J. Physiol.
258 R578–90
Bigger J T, Steinman R C, Rolnitzky L M, Fleiss J L, Albrecht P and Cohen R J 1996 Power law behavior of RR-
interval variability in healthy middle-aged persons, patients with recent acute myocardial infarction, and patients
with heart transplants Circulation 93 2142–51
Boggild H and Knutsson A 1999 Shift work, risk factors and cardiovascular disease Scand. J. Work Environ.
Health 25 85–99
Brockway B P, Mills P A and Azar S H 1991 A new method for continuous chronic measurement and recording of
blood pressure, heart rate and activity in the rat via radio-telemetry Clin. Exp. Hypertens. A13 885–95
Buijs R M, la Fleur S E, Wortel J, Van Heyningen C, Zuiddam L, Mettenleiter T C, Kalsbeek A, Nagai K and Niijima A
2003 The suprachiasmatic nucleus balances sympathetic and parasympathetic output to peripheral organs
through separate preautonomic neurons J. Comp. Neurol. 464 36–48
Conway-Campbell B L, Pooley J R, Hager G L and Lightman S L 2012 Molecular dynamics of ultradian
glucocorticoid receptor action Mol. Cell. Endocrinol. 348 383–93
Durgan D J and Young M E 2010 The cardiomyocyte circadian clock: emerging roles in health and disease Circ.
Res. 106 647–58
Eilam R, Malach R, Bergmann F and Segal M 1991 Hypertension induced by hypothalamic transplantation from
genetically hypertensive to normotensive rats J. Neurosci. 11 401–11
Hadtstein C, Wuhl E, Soergel M, Witte K and Schaefer F 2004 Normative values for circadian and ultradian
cardiovascular rhythms in childhood Hypertension 43 547–54
Herold M, Cornelissen G, Loeckinger A, Koeberle D, Koenig P and Halberg F 1998 About 8-hour variation of
circulating human endothelin-1 Peptides 19 821–5
Holstein-Rathlou N H, He J, Wagner A J and Marsh D J 1995 Patterns of blood pressure variability in normotensive
and hypertensive rats Am.J.Physiol.269 R1230–9
Hu K, Scheer F A, Buijs R M and Shea S A 2008 The endogenous circadian pacemaker imparts a scale-invariant
pattern of heart rate fluctuations across time scales spanning minutes to 24 hours J. Biol. Rhythms 23 265–73
Kawamura H, Ozawa Y, Jumabay M, Mitsubayashi H, Izumi Y, Mahmut M, Ming M Y, Aisa M, Cheng Z H
and Wang S Z 2003 Time-series analysis of systolic blood pressure variation in thirty-three Uygur centenarians
in China Hypertens. Res. 26 597–601
Koch H J, Raschka C and Banzer W 1999 Diurnal variation of ECG intervals and R or T amplitudes in healthy male
subjects assessed by means of spectral and cosinor analysis Japan. Heart J. 40 45–53
Lefcourt A M, Huntington J B, Akers R M, Wood D L and Bitman J 1999 Circadian and ultradian rhythms of
body temperature and peripheral concentrations of insulin and nitrogen in lactating dairy cows Domest. Anim.
Endocrinol. 16 41–55
Lemmer B, Mattes A, B¨
ohm M and Ganten D 1993 Circadian blood pressure variation in transgenic hypertensive rats
Hypertension 22 97–101
Makikallio A M, Makikallio T H, Korpelainen J T, Sotaniemi K A, Huikuri H V and Myllyla V V 2004 Heart rate
dynamics predict poststroke mortality Neurology 62 1822–6
Mighiu A S and Heximer S P 2012 Controlling parasympathetic regulation of heart rate: a gatekeeper role for RGS
proteins in the sinoatrial node Front. Physiol. 31–6
Mistlberger R E, de Groot M H, Bossert J M and Marchant E G 1996 Discrimination of circadian phase in intact and
suprachiasmatic nuclei-ablated rats Brain Res. 739 12–8
Molcan ˇ
L, Vesel ´
a A and Zeman M 2009 Radiotelemetry measurement of heart rate, blood pressure and locomotor
activity of rats in physiological experiment Slovak J. Anim. Sci. 42 63–6
Oosting J, Struijker-Boudier H A and Janssen B J 1997 Autonomic control of ultradian and circadian rhythms of
blood pressure, heart rate, and baroreflex sensitivity in spontaneously hypertensive rats J. Hypertens. 15 401–10
Perez-Lloret S, Aguirre A G, Cardinali D P and Toblli J E 2004 Disruption of ultradian and circadian rhythms of
blood pressure in nondipper hypertensive patients Hypertension 44 311–5
Peters R V, Zoeller R T, Hemmessey A C, Stopa E G, Anderson G and Albers H E 1994 The control of circadian
rhythms and the levels of vasoactive intestinal peptide mRNA in the suprachiasmatic nucleus are altered in
spontaneously hypertensive rats Brain Res. 639 217–27
Scheer F A, Kalsbeek A and Buijs R M 2003 Cardiovascular control by the suprachiasmatic nucleus: neural and
neuroendocrine mechanisms in human and rat Biol. Chem. 384 697–709
Schoefl C, Becker C, Prank K, von zur M¨
uhlen A and Brabant G 1997 Twenty-four-hour rhythms of
plasma catecholamines and their relation to cardiovascular parameters in healthy young men Eur. J.
Endocrinol. 137 675–83
Sheward W J, Naylor E, Knowles-Barley S, Armstrong J D, Brooker G A, Seckl J R, Turek F W, Holmes M C,
Zee P C and Harmar A J 2010 Circadian control of mouse heart rate and blood pressure by the suprachiasmatic
nuclei: behavioral effects are more significant than direct outputs PLoS One 5e9783
1632 L Molcan et al
Syrseloudis D, Tsioufis C, Aragiannis D, Soulis D, Stefanadi E, Spanos A, Mihas C, Tousoulis D, Kallikazaros I
and Stefanadis C 2011 The dominant role of the systolic component of nondipping status on target-organ damage
in never-treated hypertensives Am. J. Hypertens. 24 292–8
Wang X S, Armstrong M E, Cairns B J, Key T J and Travis R C 2011 Shift work and chronic disease: the
epidemiological evidence Occup. Med. (Lond.) 61 78–89
Warren W S, Champney T H and Cassone V M 1994 The suprachiasmatic nucleus controls the circadian rhythm of
heart rate via the sympathetic nervous system Physiol. Behav. 55 1091–9
Witte K and Lemmer B 1995 Free-running rhythms in blood pressure and heart rate in normotensive and transgenic
hypertensive rats Chronobiol. Int. 12 237–47
Witte K, Schnecko A, Buijs R M, Van der Vliet J, Scalbert E, Guardiola-Lemaˆ
ıtre B and Lemmer B 1998 Effects of
SCN lesions on circadian blood pressure rhythm in normotensive and transgenic hypertensive rats Chronobiol.
Int. 15 135–45
Yates F E and Benton L A 1991 Characteristics of ultradian and circadian rhythms of selected cardiovascularvariables.
Diagnostic and therapeutic implications Ann. NY Acad. Sci. 618 38–56
Zhang B L, Zannou E and Sannajust F 2000 Effects of photoperiod reduction on rat circadian rhythms of BP, heart
rate, and locomotor activity Am. J. Physiol. Regul. Integr. Comp. Physiol. 279 R169–78
Zuther P, Gorbey S and Lemmer B 2009 Chronos-Fit 1.06 http://www.ma.uniheidelberg.de/inst/phar/lehre/chrono.html
