Article

Circadian Control of Mouse Heart Rate and Blood Pressure by the Suprachiasmatic Nuclei: Behavioral Effects Are More Significant than Direct Outputs

Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
PLoS ONE (Impact Factor: 3.53). 03/2010; 5(3):e9783. DOI: 10.1371/journal.pone.0009783
Source: PubMed

ABSTRACT Diurnal variations in the incidence of events such as heart attack and stroke suggest a role for circadian rhythms in the etiology of cardiovascular disease. The aim of this study was to assess the influence of the suprachiasmatic nucleus (SCN) circadian clock on cardiovascular function.
Heart rate (HR), blood pressure (BP) and locomotor activity (LA) were measured in circadian mutant (Vipr2(-/-)) mice and wild type littermates, using implanted radio-telemetry devices. Sleep and wakefulness were studied in similar mice implanted with electroencephalograph (EEG) electrodes. There was less diurnal variation in the frequency and duration of bouts of rest/activity and sleep/wake in Vipr2(-/-) mice than in wild type (WT) and short "ultradian" episodes of arousal were more prominent, especially in constant conditions (DD). Activity was an important determinant of circadian variation in BP and HR in animals of both genotypes; altered timing of episodes of activity and rest (as well as sleep and wakefulness) across the day accounted for most of the difference between Vipr2(-/-) mice and WT. However, there was also a modest circadian rhythm of resting HR and BP that was independent of LA.
If appropriate methods of analysis are used that take into account sleep and locomotor activity level, mice are a good model for understanding the contribution of circadian timing to cardiovascular function. Future studies of the influence of sleep and wakefulness on cardiovascular physiology may help to explain accumulating evidence linking disrupted sleep with cardiovascular disease in man.

0 Followers
 · 
93 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Key points• The circadian system drives rhythms of behaviour, physiology and gene expression in alignment to a light–dark cycle, and misalignment of the internal clock with the external environment can lead to disease. • We sought to determine whether scheduled exercise could alter rhythmic properties in mice while subjected to the strong entrainment effects of light and whether we could improve diurnal deficits observed in the vasointestinal polypeptide (VIP)‐deficient mouse. • Scheduled exercise altered daily rhythms of activity, physiology and gene expression in wild‐type and VIP‐deficient mice. • Scheduled exercise during the late night improved many of the rhythmic deficits observed in VIP‐deficient mice, including changes in gene expression within the suprachiasmatic nucleus, the site of circadian rhythm generation. • The results raise the possibility that scheduled exercise could be a tool to drive and improve daily rhythms in humans to mitigate the negative consequences of circadian misalignment. Abstract The circadian system co‐ordinates the temporal patterning of behaviour and many underlying biological processes. In some cases, the regulated outputs of the circadian system, such as activity, may be able to feed back to alter core clock processes. In our studies, we used four wheel‐access conditions (no access; free access; early night; and late night) to manipulate the duration and timing of activity while under the influence of a light–dark cycle. In wild‐type mice, scheduled wheel access was able to increase ambulatory activity, inducing a level of exercise driven at various phases of the light–dark cycle. Scheduled exercise also manipulated the magnitude and phasing of the circadian‐regulated outputs of heart rate and body temperature. At a molecular level, the phasing and amplitude of PER2::LUCIFERASE (PER2::LUC) expression rhythms in the SCN and peripheral tissues of Per2::Luc knockin mice were altered by scheduled exercise. We then tested whether scheduled wheel access could improve deficits observed in vasointestinal polypeptide‐deficient mice under the influence of a light–dark cycle. We found that scheduled wheel access during the late night improved many of the behavioural, physiological and molecular deficits previously described in vasointestinal polypeptide‐deficient mice. Our results raise the possibility that scheduled exercise could be used as a tool to modulate daily rhythms and, when applied, may counteract some of the negative impacts of ageing and disease on the circadian system.
    The Journal of Physiology 11/2012; 590(23). DOI:10.1113/jphysiol.2012.233676 · 4.54 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Few studies have systematically investigated whether daily patterns of arterial blood pressure over 24 h are mediated by changes in cardiac output, peripheral resistance, or both. Understanding the hemodynamic mechanisms that determine the 24 h patterns of blood pressure may lead to a better understanding of how such patterns become disturbed in hypertension and influence risk for cardiovascular events. In conscious, unrestrained C57BL/6J mice, we investigated whether the 24 h pattern of arterial blood pressure is determined by variation in cardiac output, systemic vascular resistance, or both and also whether variations in cardiac output are mediated by variations in heart rate and or stroke volume. As expected, arterial pressure and locomotor activity were significantly (P < 0.05) higher during the nighttime period compared with the daytime period when mice are typically sleeping (+12.5 ± 1.0 mmHg, [13%] and +7.7 ± 1.3 activity counts, [254%], respectively). The higher arterial pressure during the nighttime period was mediated by higher cardiac output (+2.6 ± 0.3 mL/min, [26%], P < 0.05) in association with lower peripheral resistance (−1.5 ± 0.3 mmHg/mL/min, [−13%] P < 0.05). The increased cardiac output during the nighttime was mainly mediated by increased heart rate (+80.0 ± 16.5 beats/min, [18%] P < 0.05), as stroke volume increased minimally at night (+1.6 ± 0.5 μL per beat, [6%] P < 0.05). These results indicate that in C57BL/6J mice, the 24 h pattern of blood pressure is hemodynamically mediated primarily by the 24 h pattern of cardiac output which is almost entirely determined by the 24 h pattern of heart rate. These findings suggest that the differences in blood pressure between nighttime and daytime are mainly driven by differences in heart rate which are strongly correlated with differences in locomotor activity.
    11/2014; 2(11). DOI:10.14814/phy2.12223
  • [Show abstract] [Hide abstract]
    ABSTRACT: The increase in acetylcholine yielded by pyridostigmine (PYR), an acetylcholinesterase inhibitor, was evaluated for its effect on the haemodynamic responses-mean arterial pressure (MAP) and heart rate (HR)-and their nycthemeral oscillation in mice before and one week after myocardial infarction (MI). Mice were anesthetized (isoflurane), and a telemetry transmitter was implanted into the carotid artery. After 5days of recovery, the MAP and HR were recorded for 48h (10s every 10min). Following this procedure, mice were submitted to surgery for sham or coronary artery ligation and received drinking water (VEHICLE) with or without PYR. Five days after surgery, the haemodynamic recordings were recommenced. Sham surgery combined with VEHICLE did not affect basal MAP and HR; nevertheless, these haemodynamic parameters were higher during the night, before and after surgery. MI combined with VEHICLE displayed decreased MAP and increased HR; these haemodynamic parameters were also higher during the night, before and after surgery. Sham surgery combined with PYR displayed similar results for MAP as sham combined with VEHICLE; however, PYR produced bradycardia. Nevertheless, MI combined with PYR exhibited no change in MAP and HR, but these haemodynamic parameters were also higher during the night, before and after surgery. Therefore, MI decreased MAP and increased HR, while PYR prevented these alterations. Neither MI nor PYR affected nycthemeral oscillations of MAP and HR. These findings indicate that the increase in acetylcholine yielded by PYR protected the haemodynamic alterations caused by MI in mice, without affecting the nycthemeral haemodynamic oscillations. Copyright © 2014 Elsevier B.V. All rights reserved.
    Autonomic neuroscience: basic & clinical 11/2014; 187. DOI:10.1016/j.autneu.2014.11.007 · 1.37 Impact Factor

Full-text (3 Sources)

Download
34 Downloads
Available from
May 28, 2014