Evaluation of cardiovascular effects of caffeine using telemetric monitoring in the conscious rat

Ilbäck, Nils-Gunnar; Siller, M.; Stålhandske, Torbjörn

doi:10.1016/j.fct.2006.11.001

Cited by 17 publications

(14 citation statements)

References 24 publications

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“…The drug produces robust increases in arousal [25, 54, 213, 335, 488, 522] and has been shown to enhance LC activity [28, 100]. Administration of caffeine also produces increases in heart rate [194], blood pressure [194, 315, 464] and temperature [229], consistent with activation of the sympathetic nervous system. Interestingly, caffeine antagonises the sedative and autonomic effects of clonidine [417], a drug known to reduce LC activity (see 3.1, above).…”

Section: Pharmacological Alterations Of Locus Coeruleus Activitymentioning

confidence: 99%

Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part II: Physiological and Pharmacological Manipulations and Pathological Alterations of Locus Coeruleus Activity in Humans

Samuels

Szabadi²

2008

396

365

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The locus coeruleus (LC), the major noradrenergic nucleus of the brain, gives rise to fibres innervating most structures of the neuraxis. Recent advances in neuroscience have helped to unravel the neuronal circuitry controlling a number of physiological functions in which the LC plays a central role. Two such functions are the regulation of arousal and autonomic activity, which are inseparably linked largely via the involvement of the LC. Alterations in LC activity due to physiological or pharmacological manipulations or pathological processes can lead to distinct patterns of change in arousal and autonomic function. Physiological manipulations considered here include the presentation of noxious or anxiety-provoking stimuli and extremes in ambient temperature. The modification of LC-controlled functions by drug administration is discussed in detail, including drugs which directly modify the activity of LC neurones (e.g., via autoreceptors, storage, reuptake) or have an indirect effect through modulating excitatory or inhibitory inputs. The early vulnerability of the LC to the ageing process and to neurodegenerative disease (Parkinson’s and Alzheimer’s diseases) is of considerable clinical significance. In general, physiological manipulations and the administration of stimulant drugs, α2-adrenoceptor antagonists and noradrenaline uptake inhibitors increase LC activity and thus cause heightened arousal and activation of the sympathetic nervous system. In contrast, the administration of sedative drugs, including α2-adrenoceptor agonists, and pathological changes in LC function in neurodegenerative disorders and ageing reduce LC activity and result in sedation and activation of the parasympathetic nervous system.

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Section: Pharmacological Alterations Of Locus Coeruleus Activitymentioning

confidence: 99%

Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part II: Physiological and Pharmacological Manipulations and Pathological Alterations of Locus Coeruleus Activity in Humans

Samuels

Szabadi²

2008

396

365

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“…The parameters we examined were heart rate (HR), body temperature (Temp), locomotor activity (LA), and oxygen consumption (O 2 C) since they could be examined in awake animals and for prolonged periods of time. Acute or single-dose caffeine treatment mainly showed a stimulating effect on HR but clearly biphasic effects on Temp and LA (18,27,36,51). We examined not only acute effects of injecting caffeine but also the effect of adding caffeine to the drinking water for 7 days.…”

mentioning

confidence: 99%

Physiological roles of A₁ and A_2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine

Yang

Chen²,

Fredholm³

2009

American Journal of Physiology-Heart and Circulatory Physiology

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Yang JN, Chen JF, Fredholm BB. Physiological roles of A1 and A2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine. Am J Physiol Heart Circ Physiol 296: H1141-H1149, 2009. First published February 13, 2009 doi:10.1152/ajpheart.00754.2008.-Heart rate (HR), body temperature (Temp), locomotor activity (LA), and oxygen consumption (O2C) were studied in awake mice lacking one or both of the adenosine A 1 or A2A receptors (A1R or A2AR, respectively) using telemetry and respirometry, before and after caffeine administration. All parameters were lower during day than night and higher in females than males. When compared with wild-type (WT) littermates, HR was higher in male A 1R knockout (A1RKO) mice but lower in A2ARKO mice and intermediate in A1-A2AR double KO mice. A single dose of an unselective ␤-blocker (timolol; 1 mg/kg) abolished the HR differences between these genotypes. Deletion of A 1Rs had little effect on Temp, whereas deletion of A 2ARs increased it in females and decreased it in males. A 1-A2ARKO mice had lower Temp than WT mice. LA was unaltered in A 1RKO mice and lower in A 2ARKO and A1-A2ARKO mice than in WT mice. Caffeine injection increased LA but only in mice expressing A 2AR. Caffeine ingestion also increased LA in an A 2AR-dependent manner in male mice. Caffeine ingestion significantly increased O 2C in WT mice, but less in the different KO mice. Injection of 30 mg/kg caffeine decreased Temp, especially in KO mice, and hence in a manner unrelated to A 1R or A 2AR blockade. Selective A2B antagonism had little or no effect. Thus A 1R and A2AR influence HR, Temp, LA, and O2C in mice in a sex-dependent manner, indicating effects of endogenous adenosine. The A2AR plays an important role in the modulation of O2C and LA by acute and chronic caffeine administration. There is also evidence for effects of higher doses of caffeine being independent of both A 1R and A2AR. diurnal rhythm; metabolic rate; locomotor activity; adenosine; telemetry CAFFEINE (1,3,7-trimethylxanthine), the most widely consumed stimulant in the world, acts as a competitive antagonist of adenosine receptors (ARs) (18). It is much more potent on three of the known receptors, A 1 , A 2A , and A 2B (A 1 R, A 2A R, and A 2B R, respectively) than on the fourth, the A 3 R (17). Since a competitive antagonist will have effects only when and where receptors are activated by an agonist, it is relevant that endogenous agonist adenosine is more potent on A 1 R and A 2A R than on A 2B R. The potency of adenosine as an agonist in addition depends on the density of the receptors (16). The levels of adenosine are low under physiological condition but are sufficient to partially activate A 1 R, A 2A R, and A 3 Rs where the receptors are abundantly expressed. For these reasons caffeine is generally believed to act on A 1 R and A 2A R to exert most of its effects, at least when given in lower doses (18). However, a recent study showed that A 2B R knockout (A 2B RKO) mice have e...

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“…A number of factors, aside from CVdrift, have the potential to contribute to elevations in resting and exercise HR, such as sympathetic nervous system activation resulting from caffeine ingestion, increased core temperature, or stress,31 32 33 and such factors would likely influence HR early during exercise. Furthermore, because CVdrift does not occur until >10 min beyond the onset of exercise, we also assumed that CVdrift sufficient to drive HR beyond the desired range would not occur between minute 10 and minute 12 of exercise, and therefore, in cases of CVdrift, METS would remain unchanged prior to minute 12 of exercise.…”

Section: Methodsmentioning

confidence: 99%

Heart rate and exercise intensity during training: observations from the DREW Study

et al. 2008

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Evaluation of cardiovascular effects of caffeine using telemetric monitoring in the conscious rat

Cited by 17 publications

References 24 publications

Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part II: Physiological and Pharmacological Manipulations and Pathological Alterations of Locus Coeruleus Activity in Humans

Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part II: Physiological and Pharmacological Manipulations and Pathological Alterations of Locus Coeruleus Activity in Humans

Physiological roles of A₁ and A_2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine

Heart rate and exercise intensity during training: observations from the DREW Study

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