scholarly journals Role of mutation of the circadian clock gene Per2 in cardiovascular circadian rhythms

2010 ◽  
Vol 298 (3) ◽  
pp. R627-R634 ◽  
Author(s):  
Ana Vukolic ◽  
Vladan Antic ◽  
Bruce N. Van Vliet ◽  
Zhihong Yang ◽  
Urs Albrecht ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Locomotor Activity ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Mutant Mice ◽  
Constant Darkness ◽  
Wild Type ◽  
Chi Square ◽  
Dark Light

Alterations in the circadian blood pressure pattern are frequently observed in hypertension and lead to increased cardiovascular morbidity. However, there are no studies that have investigated a possible implication of the Period2 gene, a key component of the molecular circadian clock, on the circadian rhythms of blood pressure and heart rate. To address this question, we monitored blood pressure, heart rate, and locomotor activity 24 h a day by telemetry in mice carrying a mutation in the Period2 gene and in wild-type control mice. Under a standard 12:12-h light-dark cycle, mutant mice showed a mild cardiovascular phenotype with an elevated 24-h heart rate, a decreased 24-h diastolic blood pressure, and an attenuation of the dark-light difference in blood pressure and heart rate. Locomotor activity was similar in both groups and did not appear to explain the observed hemodynamic differences. When mice were placed under constant darkness during eight consecutive days, wild-type mice maintained 24-h rhythms, whereas there was an apparent progressive loss of 24-h rhythm of blood pressure, heart rate, and locomotor activity in mutant mice. However, a chi square periodogram revealed that circadian rhythms were preserved under complete absence of any light cue, but with shorter periods by ∼40 min, leading to a cumulative phase shift toward earlier times of ∼5 h and 20 min by the end of the 8th day. When heart rate, mean arterial pressure, and activity were recalculated according to the endogenous circadian periods of each individual mouse, the amplitudes of the circadian rhythms (“subjective night”-“subjective day” differences) were maintained for all variables studied. Our data show that mutation of the Period2 gene results in an attenuated dipping of blood pressure and heart rate during both light-dark cycles and constant darkness, and in shorter circadian periods during constant darkness.

scholarly journals Effects of Suprachiasmatic Lesions on Circadian Rhythms of Blood Pressure, Heart Rate and Locomotor Activity in the Rat.

1995 ◽  
Vol 59 (8) ◽  
pp. 565-573 ◽  
Author(s):  
Hiroaki Sano ◽  
Hiroshi Hayashi ◽  
Mitsutaka Makino ◽  
Hiroto Takezawa ◽  
Makoto Hirai ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Locomotor Activity ◽  
Circadian Rhythms

Effects of photoperiod reduction on rat circadian rhythms of BP, heart rate, and locomotor activity

2000 ◽  
Vol 279 (1) ◽  
pp. R169-R178 ◽  
Author(s):  
Bei-Li Zhang ◽  
Erika Zannou ◽  
Frédéric Sannajust
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Locomotor Activity ◽  
Circadian Rhythms ◽  
Wistar Rats ◽  
Dark Period ◽  
Dark Phase ◽  
Mean Values ◽  
Shift Response ◽  
H 20

The effects of a photoperiod reduction in the entrainment of circadian rhythms of systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and spontaneous locomotor activity (SLA) were determined in conscious Wistar rats by using radiotelemetry. Two groups of seven rats were maintained in a 12:12-h light-dark (12L/12D) photoperiod for 11 wk and then placed in a reduced photoperiod of 8:16-h light-dark (8L/16D) by advancing a 4-h darkness or by advancing and delaying a 2-h darkness for 6 wk. Finally, they were resynchronized to 12L/12D. Advancing a 4-h dark phase induced a 1-h advance of acrophase for SBP, DBP, and HR, but not for SLA. The percent rhythm, amplitude, and the 12-h mean values of all parameters were significantly decreased by the photoperiod reduction. When symmetrically advancing and delaying a 2-h dark phase, a 1 h 20 min delay of acrophases and a decrease in percent rhythms and amplitudes of SBP, DBP, HR, and SLA were observed. Only the 12-h mean values of HR and SLA were decreased. Our findings show that the cardiovascular parameters differ from SLA in phase-shift response to photoperiod reduction and that the adjustment of circadian rhythms to change from 12L/12D to 8L/16D photoperiod depends on the direction of the extension of the dark period.

Interruption of the rat circadian clock by short light-dark cycles

2003 ◽  
Vol 284 (5) ◽  
pp. R1255-R1259 ◽  
Author(s):  
Setsuo Usui ◽  
Terue Okazaki ◽  
Yoshiko Honda
Keyword(s):  
Locomotor Activity ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Constant Darkness ◽  
Sprague Dawley ◽  
Light Stimulation ◽  
Behavioral Rhythms ◽  
Light Pulses ◽  
Sprague Dawley Rats

Ninety male Sprague-Dawley rats were exposed to 1:1-h light-dark (LD1:1) cycles for 50–90 days, and then they were released into constant darkness (DD). During LD1:1 cycles, behavioral rhythms were gradually disintegrated, and circadian rhythms of locomotor activity, drinking, and urine 6-sulfatoxymelatonin excretion were eventually abolished. After release into DD, 44 (49%) rats showed arrhythmic behavior for >10 days. Seven (8%) animals that remained arrhythmic for >50 days in DD were exposed to brief light pulses or 12:12-h light-dark cycles, and then they restored their circadian rhythms. These results indicate that the circadian clock was stopped, at least functionally, by LD1:1 cycles and was restarted by subsequent light stimulation.

Disrupted circadian rhythms in VIP- and PHI-deficient mice

2003 ◽  
Vol 285 (5) ◽  
pp. R939-R949 ◽  
Author(s):  
Christopher S. Colwell ◽  
Stephan Michel ◽  
Jason Itri ◽  
Williams Rodriguez ◽  
J. Tam ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Wheel Running ◽  
Activity Rhythm ◽  
Activity Patterns ◽  
Circadian System ◽  
Diurnal Rhythms ◽  
Constant Darkness ◽  
Light Cycle ◽  
Wild Type ◽  
Deficient Mice

The related neuropeptides vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are expressed at high levels in the neurons of the suprachiasmatic nucleus (SCN), but their function in the regulation of circadian rhythms is unknown. To study the role of these peptides on the circadian system in vivo, a new mouse model was developed in which both VIP and PHI genes were disrupted by homologous recombination. In a light-dark cycle, these mice exhibited diurnal rhythms in activity which were largely indistinguishable from wild-type controls. In constant darkness, the VIP/PHI-deficient mice exhibited pronounced abnormalities in their circadian system. The activity patterns started ∼8 h earlier than predicted by the previous light cycle. In addition, lack of VIP/PHI led to a shortened free-running period and a loss of the coherence and precision of the circadian locomotor activity rhythm. In about one-quarter of VIP/PHI mice examined, the wheel-running rhythm became arrhythmic after several weeks in constant darkness. Another striking example of these deficits is seen in the split-activity patterns expressed by the mutant mice when they were exposed to a skeleton photoperiod. In addition, the VIP/PHI-deficient mice exhibited deficits in the response of their circadian system to light. Electrophysiological analysis indicates that VIP enhances inhibitory synaptic transmission within the SCN of wild-type and VIP/PHI-deficient mice. Together, the observations suggest that VIP/PHI peptides are critically involved in both the generation of circadian oscillations as well as the normal synchronization of these rhythms to light.

scholarly journals Salt sensitivity of blood pressure in NKCC1-deficient mice

2008 ◽  
Vol 295 (4) ◽  
pp. F1230-F1238 ◽  
Author(s):  
Soo Mi Kim ◽  
Christoph Eisner ◽  
Robert Faulhaber-Walter ◽  
Diane Mizel ◽  
Susan M. Wall ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Wheel Running ◽  
Plasma Renin ◽  
Pressure Change ◽  
Standard Diet ◽  
Wild Type ◽  
Vascular Effects ◽  
Arterial Blood ◽  
Deficient Mice

NKCC1 is a widely expressed isoform of the Na-2Cl-K cotransporter that mediates several direct and indirect vascular effects and regulates expression and release of renin. In this study, we used NKCC1-deficient (NKCC1−/−) and wild-type (WT) mice to assess day/night differences of blood pressure (BP), locomotor activity, and renin release and to study the effects of high (8%) or low (0.03%) dietary NaCl intake on BP, activity, and the renin/aldosterone system. On a standard diet, 24-h mean arterial blood pressure (MAP) and heart rate determined by radiotelemetry, and their day/night differences, were not different in NKCC1−/− and WT mice. Spontaneous and wheel-running activities in the active night phase were lower in NKCC1−/− than WT mice. In NKCC1−/− mice on a high-NaCl diet, MAP increased by 10 mmHg in the night without changes in heart rate. In contrast, there was no salt-dependent blood pressure change in WT mice. MAP reductions by hydralazine (1 mg/kg) or isoproterenol (10 μg/mouse) were significantly greater in NKCC1−/− than WT mice. Plasma renin (PRC; ng ANG I·ml−1·h−1) and aldosterone (aldo; pg/ml) concentrations were higher in NKCC1−/− than WT mice (PRC: 3,745 ± 377 vs. 1,245 ± 364; aldo: 763 ± 136 vs. 327 ± 98). Hyperreninism and hyperaldosteronism were found in NKCC1−/− mice during both day and night. High Na suppressed PRC and aldosterone in both NKCC1−/− and WT mice, whereas a low-Na diet increased PRC and aldosterone in WT but not NKCC1−/− mice. We conclude that 24-h MAP and MAP circadian rhythms do not differ between NKCC1−/− and WT mice on a standard diet, probably reflecting a balance between anti- and prohypertensive factors, but that blood pressure of NKCC1−/− mice is more sensitive to increases and decreases of Na intake.

scholarly journals Wild-Type Circadian Rhythmicity Is Dependent on Closely Spaced E Boxes in the Drosophila timelessPromoter

2001 ◽  
Vol 21 (4) ◽  
pp. 1207-1217 ◽  
Author(s):  
Michael J. McDonald ◽  
Michael Rosbash ◽  
Patrick Emery
Keyword(s):  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Locomotor Activity ◽  
Circadian Rhythms ◽  
High Amplitude ◽  
Wild Type ◽  
Activity Rhythms ◽  
E Box ◽  
E Boxes ◽  
Circadian Transcription

ABSTRACT Transcriptional regulation plays an important role inDrosophila melanogaster circadian rhythms. The period promoter has been well studied, but the timeless promoter has not been analyzed in detail. Mutagenesis of the canonical E box in the timelesspromoter reduces but does not eliminate timeless mRNA cycling or locomotor activity rhythms. This is because there are at least two other cis-acting elements close to the canonical E box, which can also be transactivated by the circadian transcription factor dCLOCK. These E-box-like sequences cooperate with the canonical E-box element to promote high-amplitude transcription, which is necessary for wild-type rhythmicity.

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