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Repeated Phase Shifts in the Lighting Regimen Change the Blood Pressure Response to Norepinephrine Stimulation in Rats

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Abstract

Disturbed circadian activity of the sympathetic system may be involved in negative consequences of chronodisruption on the cardiovascular system. We studied daily changes in pressure response to adrenergic stimulation in rats exposed to repeated phase advance shifts (PAS) of light/dark (LD) regimen. Blood pressure (BP), heart rate (HR) and locomotor activity was measured by radiotelemetry in normotensive Wistar rats exposed to repeated PAS (three 8-h shifts per week) lasting for 12 weeks. Norepinephrine was administered subcutaneously in the middle of L and D during week 12 of PAS exposure. In the control LD cycle, cardiovascular parameters exhibited significant daily rhythms with expected higher values during D than L phase. Rats exposed to PAS showed disturbed rhythms without a BP and HR increase. Administration of norepinephrine to control rats revealed daily variability in the cardiovascular response with higher stimulation of BP during L than D. This daily pattern of BP response to norepinephrine was diminished in the PAS group. The damped daily variability in pressure response to norepinephrine and augmented response during the light phase of the day suggest that the increased and desynchronised activity of the sympathetic system may worsen responses of the cardiovascular system to load in individuals exposed to irregular LD conditions.
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... In rats exposed to a regular lightdark regime, noradrenaline elicits a higher blood pressure response during the light (passive) phase than the dark (active) phase. However, this phase-dependent response is lost under ALAN conditions, with blood pressure exhibiting a significantly increased response to noradrenaline even during the dark phase [55,56,82]. There are several hypotheses for this phenomenon: (1) The first is related to vascular tone, which is significantly controlled by the sympathetic nervous system. ...
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Artificial light at night (ALAN) affects most of the population. Through the retinohypothalamic tract, ALAN modulates the activity of the central circadian oscillator and, consequently, various physiological systems, including the cardiovascular one. We summarised the current knowledge about the effects of ALAN on the cardiovascular system in diurnal and nocturnal animals. Based on published data, ALAN reduces the day-night variability of the blood pressure and heart rate in diurnal and nocturnal animals by increasing the nocturnal values of cardiovascular variables in diurnal animals and decreasing them in nocturnal animals. The effects of ALAN on the cardiovascular system are mainly transmitted through the autonomic nervous system. ALAN is also considered a stress-inducing factor, as glucocorticoid and glucose level changes indicate. Moreover, in nocturnal rats, ALAN increases the pressure response to load. In addition, ALAN induces molecular changes in the heart and blood vessels. Changes in the cardiovascular system significantly depend on the duration of ALAN exposure. To some extent, alterations in physical activity can explain the changes observed in the cardiovascular system after ALAN exposure. Although ALAN acts differently on nocturnal and diurnal animals, we can conclude that both exhibit a weakened circadian coordination among physiological systems, which increases the risk of future cardiovascular complications and reduces the ability to anticipate stress.
... However, HR exhibits circadian fluctuations, and values measured at specific times of the day should reasonably be accepted. The reason for such an approach is the fact that telemetry studies in awake rats indicate the existence of a circadian rhythm in HR, not only in males (Hashimoto et al., 1999(Hashimoto et al., , 2001Koresh et al., 2016;Molcan et al., 2013Molcan et al., , 2014Wessel et al., 2007) but also in females (Koresh et al., 2016;Schlatter & Zbinden, 1982). Therefore, in this regard, the use of the HRV method can be an effective and non-invasive tool for the assessment of autonomic control of the heart, as well as autonomic modulation of HR (Akselrod, 1988;Lunqvist, 1990;Malik & Camm, 1993;Mansier et al., 1996), for which changes are a useful indicator of tendencies F I G U R E 1 Graphical representation of sex differences in individual heart rate variability (HRV) parameters depending on the light-dark (LD) cycle in rats under zoletil anaesthesia. ...
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Heart rate variability (HRV) is commonly used in experimental studies to assess sympathetic and parasympathetic activities. The belief that HRV in rodents reflects similar cardiovascular regulations in humans is supported by evidence, and HRV in rats appears to be at least analogous to that in humans, although the degree of influence of the parasympathetic division of the autonomic nervous system (ANS) may be greater in rats than in humans. Experimental studies are based on control or baseline values, on the basis of which the change in ANS activity after a given experimental intervention is assessed, but it is known that the ANS in rats is very sensitive to various stress interventions, such as the manipulation itself, and ANS activity can also differ depending on sex, the time of measurement, and whether the animals are under general anaesthesia. Thus, for correct assessment, changes in ANS activity and their relationship to the observed parameter should be based on whether ANS activity does or does not change but also to what extent the activity is already changed at the start of the experiment. Since rats are considered to be the most suitable model animal for basic cardiovascular research, in this review we point out existing differences in individual HRV frequency parameters at the start of experiments (control, baseline values), taking into account sex in relation to time of measurement and anaesthesia.
... Our results, therefore, indicate that in zoletil-anesthetized rats, LD differences were maintained only in males but not in females. Considering the results of telemetry studies by Molcan et al. [50,51], heart rate exhibits a significant circadian rhythm in non-anesthetized rats, in which the heart rate in the dark period fluctuated from 347 beats/min to 363 beats/min, and from 309 beats/min to 321 beats/min in the light period. Thus, it appears that although zoletil exerts a tachycardic effect, [7,30,31]; pent -Pentobarbital (161.1(156.1-165.7), ...
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The aim was to evaluate the current state of the autonomic nervous system (ANS) activity under general anesthesia using heart rate variability (HRV) in dependence on the light-dark (LD) cycle in healthy, sexually mature, spontaneously breathing, zoletil-anesthetized (30 mg/kg) Wistar rats of both sexes after a 4-week adaptation to an LD cycle (12 h:12 h). The animals were divided into four experimental groups according to sex and light period (n = 20 each). RR interval duration, spectral power at very-low-frequency (VLF), low-frequency (LF) and high-frequency (HF), total spectral power of HRV, and the LF/HF ratio were analyzed. Sympathetic and baroreceptor activity was decreased, and parasympathetic activity was increased in both sexes and in both light periods. Regarding sex differences, HRV was significantly lower in females versus males in the light period. In the dark period, females exhibited higher HRV than males. Regarding LD differences, in females, HRV was lower in the light versus the dark period, unlike males, in which HRV was higher in the dark versus the light period of the rat regimen day. Sex differences in the activity of the ANS were apparent in rats, persisted under general anesthesia, and were dependent on the LD cycle.
... Baseline HR analysis from telemetry studies involving non-anesthetized rats, in which a chronobiological approach was applied, indicates that there is a circadian rhythm in HR among rats, with a higher HR during the active (i.e., dark) period of the regimen day and not only in males [13][14][15][16][17] but also in females [15,18]. If HR exhibits circadian fluctuations, then when it is evaluated, it can be problematic. ...
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General anesthesia is an established and well-known factor with a significant impact on cardiac parameters, which can be a problem in the final evaluation of changes in the individual electrophysiological myocardial parameters after various interventions. The present chapter provides a composite review of published data on electrocardiographic parameters (heart rate, PR interval, P wave duration, P wave amplitude, QRS complex, QT and QTc interval duration, and R wave and T wave amplitude) for in vivo rat experiments under general anesthesia from 130 articles, which were retrieved from a search of the Web of Science database, for articles published mainly between 2000 and 2021. ECG parameters reported as baseline or control values were summarized, and averages with ranges were calculated. It is important to be cautious in interpreting the results of such studies and discussions addressing the mechanisms underlying a given type of arrhythmia, it is important to acknowledge that initial ECG parameters may already be affected to some extent by general anesthesia as well as by sex and the time of day the experiments are performed. Although it is not an original research work, researchers working with rats in the laboratory, who routinely perform anesthesia, can use this as a reference to look into while analyzing their data.
... Baseline HR analysis from telemetry studies involving non-anesthetized rats, in which a chronobiological approach was applied, indicates that there is a circadian rhythm in HR in rats, with a higher HR during the active (i.e., dark) period of the regimen day, not only in males [10][11][12][13][14] but also in females [12,15]. If HR exhibits circadian fluctuations, then when exactly HR is evaluated can be problematic. ...
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In in vivo cardiovascular or toxicological studies involving rat models, changes in selected electrocardiographic (ECG) parameters are monitored after various interventions to assess the origin and development of heart rhythm disorders. Each ECG parameter has diagnostic significance; as such, commonly evaluated ECG parameters, including heart rate, PR interval, P wave duration, P wave amplitude, QRS complex, QT and QTc interval duration, R wave and T wave amplitude, of rats under various types of general anesthesia were the focus of this study. Studies that performed in vivo cardiovascular or toxicological experiments in rats were retrieved from a search of the Web of Science database for articles published mainly between 2000 and 2021. In total, the search retrieved 123 articles. ECG parameters that were reported as baseline or control values were summarized and averages with ranges were calculated. It is important to be cautious when interpreting results and, in discussions addressing the mechanisms underlying a given type of arrhythmia, acknowledge that initial ECG parameters may already be affected to some extent by the general anesthesia as well as by sex and the time of day the experiments were performed.
... Our results, therefore, indicate that in zoletil-anesthetized rats, LD differences were maintained only in males but not in females. Considering the results of telemetric studies by Molcan et al. [19,20], heart rate exhibits a significant circadian rhythm in non-anesthetized rats, in which the heart rate in the dark period fluctuates from 347 beats/min to 363 beats/min, and from 309 beats/min to 321 beats/min in the light period. Thus, it appears that although zoletil exerts a tachycardic effect, it can eliminate-or, at least modify-circadian rhythm of heart rate, but only in females. ...
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Full-text available
Background: It is known that general anesthesia weakens autonomic function and baroreflex control. Intravenous anesthetics may have different qualitative and quantitative effects on the peripheral autonomic nervous system (ANS) and, can thus, alter the activity of sympathetic or parasympathetic divisions of the ANS. Presently, there are relatively little data regarding sex differences in ANS activity or sex differences in ANS activities during anesthesia. The primary goal of the present study was to assess sex differences in ANS activity in dependence on the light-dark (LD) cycle in healthy, sexually mature, spontaneously breathing zoletil-anesthetized rats.
... Our results, therefore, indicate that in zoletil-anesthetized rats, LD differences were maintained only in males but not in females. Considering the results of telemetric studies by Molcan et al. [19,20], heart rate exhibits a significant circadian rhythm in non-anesthetized rats, in which the heart rate in the dark period fluctuates from 347 beats/min to 363 beats/min, and from 309 beats/min to 321 beats/min in the light period. Thus, it appears that although zoletil exerts a tachycardic effect, it can eliminate-or, at least modify-circadian rhythm of heart rate, but only in females. ...
Article
Full-text available
Background: It is known that general anesthesia weakens autonomic function and baroreflex control. Intravenous anesthetics may have different qualitative and quantitative effects on the peripheral autonomic nervous system (ANS) and, can thus, alter the activity of sympathetic or parasympathetic divisions of the ANS. Presently, there are relatively little data regarding sex differences in ANS activity or sex differences in ANS activities during anesthesia. The primary goal of the present study was to assess sex differences in ANS activity in dependence on the light-dark (LD) cycle in healthy, sexually mature, spontaneously breathing zoletil-anesthetized rats.
... Our results, therefore, indicate that in zoletil-anesthetized rats, LD differences were maintained only in males but not in females. Considering the results of telemetry studies by Molcan et al. [50,51], heart rate exhibits a significant circadian rhythm in non-anesthetized rats, in which the heart rate in the dark period fluctuated from 347 beats/min to 363 beats/min, and from 309 beats/min to 321 beats/min in the light period. Thus, it appears that although zoletil exerts a tachycardic effect, [7,30,31]; pent -Pentobarbital (161.1(156.1-165.7), ...
Chapter
Full-text available
The aim was to evaluate the current state of the autonomic nervous system (ANS) activity under general anesthesia using heart rate variability (HRV) in dependence on the light-dark (LD) cycle in healthy, sexually mature, spontaneously breathing, zoletil-anesthetized (30 mg/kg) Wistar rats of both sexes after a 4-week adaptation to an LD cycle (12 h:12 h). The animals were divided into four experimental groups according to sex and light period (n = 20 each). RR interval duration, spectral power at very-low-frequency (VLF), low-frequency (LF) and high-frequency (HF), total spectral power of HRV, and the LF/HF ratio were analyzed. Sympathetic and baroreceptor activity was decreased, and parasympathetic activity was increased in both sexes and in both light periods. Regarding sex differences, HRV was significantly lower in females versus males in the light period. In the dark period, females exhibited higher HRV than males. Regarding LD differences, in females, HRV was lower in the light versus the dark period, unlike males, in which HRV was higher in the dark versus the light period of the rat regimen day. Sex differences in the activity of the ANS were apparent in rats, persisted under general anesthesia, and were dependent on the LD cycle.
... Our results, therefore, indicate that in zoletil-anesthetized rats, LD differences were maintained only in males but not in females. Considering the results of telemetric studies by Molcan et al. [19,20], heart rate exhibits a significant circadian rhythm in non-anesthetized rats, in which the heart rate in the dark period fluctuates from 347 beats/min to 363 beats/min, and from 309 beats/min to 321 beats/min in the light period. Thus, it appears that although zoletil exerts a tachycardic effect, it can eliminate-or, at least modify-circadian rhythm of heart rate, but only in females. ...
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