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: 3.23). 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.

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    • "previous findings in smaller rodents, including laboratory rats (Sei et al. 1997) and mice (Sei et al. 2008; Sheward et al. 2010). The overall diurnal rhythm of the HR observed in the current study was less robust than those reported for the rectal temperature (Dzenda et al. 2011a) and respiratory rate (Dzenda et al. 2015) in the AGR; assenting with the appraisal by Mortola and Lanthier (2004) of the amplitudes of circadian patterns in many mammals, including rats and mice. "
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    • "This conclusion is supported by studies demonstrating that SCNX animals lack 24-h BP rhythms but show higher BP variability (Sano et al., 1995) and, as also presented here, do not exhibit a change in basal BP. Furthermore, recent findings demonstrate that VIPr2À/À mice fail to show a circadian BP rhythm in constant conditions showing that an adequate SCN output is essential for regulation of 24-h BP rhythmicity (Sheward et al., 2010). We do not know how the output of the SCN may moderate increases in BP; it might be via its projections to pre-autonomic neurons in the hypothalamus or possibly via its projections to the NTS itself, allowing it to alter baroreflex sensitivity (Scheer et al., 2010; Shea et al., 2011); therefore more research needs to be done to explore the plurality of this NTS signal and its exact effect within the SCN. "
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    ABSTRACT: The suprachiasmatic nucleus (SCN) is typically considered our autonomous clock synchronizing behavior with physiological parameters such as blood pressure, just transmitting time independent of physiology. Yet several studies show that the SCN is involved in the etiology of hypertension. Here, we demonstrate that the SCN is incorporated in a neuronal feedback circuit arising from the nucleus tractus solitarius (NTS), modulating cardiovascular reactivity. Tracer injections into the SCN of male Wistar rats revealed retrogradely filled neurons in the caudal NTS, where blood pressure (BP) information is integrated. These NTS projections to the SCN were shown to be glutamatergic and to terminate in the ventrolateral part of the SCN where also light information enters. BP elevations not only induced increased neuronal activity as measured by c-Fos in the NTS but also in the SCN. Lesioning the caudal NTS prevented this activation. The increase of SCN neuronal activity by hypertensive stimuli suggested involvement of the SCN in counteracting BP elevations. Examining this possibility we observed that elevation of BP, induced by α1-agonist infusion, was more than twice the magnitude in SCN-lesioned animals as compared to in controls, indicating indeed an active involvement of the SCN in short-term BP regulation. We propose that the SCN receives BP information directly from the NTS enabling it to react to hemodynamic perturbations, suggesting the SCN to be part of a homeostatic circuit adapting BP response. We discuss how these findings could explain why lifestyle conditions violating signals of the biological clock may, in the long-term, result in cardiovascular disease.
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    • "This conclusion is supported by studies demonstrating that SCNX animals lack 24-h BP rhythms but show higher BP variability (Sano et al., 1995) and, as also presented here, do not exhibit a change in basal BP. Furthermore, recent findings demonstrate that VIPr2À/À mice fail to show a circadian BP rhythm in constant conditions showing that an adequate SCN output is essential for regulation of 24-h BP rhythmicity (Sheward et al., 2010). We do not know how the output of the SCN may moderate increases in BP; it might be via its projections to pre-autonomic neurons in the hypothalamus or possibly via its projections to the NTS itself, allowing it to alter baroreflex sensitivity (Scheer et al., 2010; Shea et al., 2011); therefore more research needs to be done to explore the plurality of this NTS signal and its exact effect within the SCN. "
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    Full-text · Article · Jan 2014 · Neuroscience
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