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Symposium Report |
1 Department of Environmental Health, Life Science and Human Technology, Nara Women's University, Kita-Uoya Nishimachi, Nara, 630-8506, Japan
Abstract
The responses of renal and lumbar sympathetic outflow to changes in behavioural states were reviewed in this paper. During rapid eye movement (REM) sleep, renal sympathetic nerve activity was decreased while lumbar sympathetic nerve activity increased. These diverse changes in sympathetic nerve activity observed during REM sleep help explain the responses in regional blood flow to REM sleep; that is renal blood flow increased while muscle blood flow decreased. By contrast, exercise increased both renal and muscle sympathetic nerve activity. The degree of physical activity was correlated with the magnitude of the increases in renal and muscle sympathetic nerve activity. There was a significant (P < 0.05) linear relationship between renal sympathetic nerve activity and systemic arterial pressure over the transition between non-rapid eye movement (NREM) sleep, quiet awake, moving and grooming states in the rats. This suggests that sympathetic outflows seem to be modulated quantitatively to meet cardiovascular demand caused by changes in the level of physical activity. It is therefore concluded that sympathetic outflow seems to be regulated in a state-specific manner during sleep and exercise.
(Received 16 November 2004;
accepted after revision 14 December 2004; first published online 16 December 2004)
Corresponding author K. Miki: Department of Environmental Health, Life Science and Human Technology, Nara Women's University, Kita Uoya-Nishimachi, Nara 630-8506, Japan. Email: k.miki{at}cc.nara-wu.ac.jp
Sympathetic nerves innervate most of the organs within the body, and are involved in the maintenance of the internal body homeostasis in our daily activity, including sleep, wakefulness and exercise. Cannon (1953) proposed the concept that the sympathetic innervation of the cardiovascular system generally responds in a diffuse and generalized manner. This concept has been accepted widely. However, Cannon's concept was originally derived from studies of endocrine metabolic function, but was influenced only to a minor extent by circulatory control function.
Since that time there have been fragmentary reports that regional differences in sympathetic outflows controlling vasomotor activity take place. For instance, Simon & Riedel (1975) reported a diversity of regional sympathetic outflows, which were consistent with regional cardiovascular changes during spinal cooling in anaesthetized and paralysed rabbits. Futuro-Neto & Coote (1982) demonstrated diverse changes in sympathetic nerve activity during rapid eye movement (REM) sleep-like periods induced by physostigmine sulphate in mid-collicular decerebrate cats, which partly explained the changes in regional blood flow during REM sleep; that is, decreased skeletal muscle blood flow and increased blood flow to the kidney and mesentery (Baccelli et al. 1974; Morrison, 2001; Miki et al. 2004; Yoshimoto et al. 2004). Morrison (2001) has highlighted in his review evidence for regional variations in the pattern of sympathetic outflow consequent to external stimuli, including electrical stimulation, thermal stimulation, acute exposure to hypoxia and injection of drugs.
However, the majority of previous studies investigating the regional differences in sympathetic outflow have been carried out in acutely prepared anaesthetized animals. As it is accepted that anaesthetics affect functions of the central nervous system, it is very important to know whether the patterning of sympathetic outflow occurs in a regionally different manner in conscious states. We have therefore reviewed in this paper, responses in renal and lumbar sympathetic outflow which take place during daily activity.
Diverse changes in sympathetic nerve activity during REM sleep
Direct measurement of sympathetic nerve activity during REM sleep has been performed in humans and in animals, and it has been shown that changes in sympathetic nerve activity during REM sleep are unidirectional. Sympathetic nerve outflow to the muscle vasculature during REM sleep has been measured in man using microneurography, and it was consistently found to increase during REM sleep (Hornyak et al. 1991; Okada et al. 1991; Somers et al. 1993). In support of these observations in man, lumbar sympathetic nerve outflow (L3–L4), which innervates mostly the hindquarter muscle and skin, increased significantly (P < 0.05) in a stepwise manner during REM sleep in rats (Miki et al. 2004). By contrast to the changes in muscle sympathetic nerve activity, Baust et al. (1968) using the cat were the first to show a reduction of renal sympathetic nerve activity during REM sleep, which was also found by Iwamura et al. (1969) in cats. This fact has been confirmed recently in rats in that REM sleep resulted in an immediate and sustained reduction of renal sympathetic nerve activity (Miki et al. 2003a; Yoshimoto et al. 2004).
Simultaneous measurement of sympathetic outflows to the different organs within the same animal has been attempted. In 1982, Futuro-Neto & Coote reported the existence of regional differences in sympathetic outflow during REM sleep in acutely prepared cats. They demonstrated that there were reductions in the activities of the greater splanchnic nerve, inferior cardiac nerve and renal nerve, while there was increased activity in sympathetic fibres to the gastrocnemius muscle during desynchronized sleep-like periods induced by physostigmine in decerebrated cats. The observation of an increase in sympathetic nerve activity to the gastrocnemius demonstrated by these investigators agreed well with the reports of an increase in muscle sympathetic nerve activity during REM sleep in humans (Hornyak et al. 1991; Okada et al. 1991; Somers et al. 1993) and lumbar sympathetic nerve activity (L3–L4 level) in rats (Miki et al. 2004). The decrease in renal and inferior cardiac sympathetic nerve activity reported by Futuro-Neto & Coote (1982) was comparable to that reported in intact cats (Baust et al. 1968; Iwamura et al. 1969) and in rats (Miki et al. 2003a; Yoshimoto et al. 2004). Yoshimoto et al. (2003) have succeeded in measuring renal and lumbar sympathetic nerve activity simultaneously in rats and demonstrated that a reduction in renal sympathetic nerve activity occurred concomitantly with a rise in lumbar sympathetic nerve activity during REM sleep, which was consistent with the observation by Futuro-Neto & Coote (1982). These observations clearly show that sympathetic responses to REM sleep are not unidirectional but are different across different organs.
The diverse changes in sympathetic nerve activity could well explain responses of regional blood flow to REM sleep. Thus, REM sleep induced increases in blood flow to the kidney, splanchnic organs and brain in rabbit and rats (Cianci et al. 1991; Osborne, 1997; Yoshimoto et al. 2004). Moreover, Yoshimoto et al. (2004) measured renal sympathetic nerve activity and renal blood flow simultaneously in rats, and showed that the significant increase in renal blood flow was associated with a significant (P < 0.05) reduction in renal sympathetic nerve activity. They further demonstrated that renal denervation abolished the increase in renal blood flow during REM sleep. It is therefore likely that renal sympathetic nerve activity exerts a tonic influence on renal blood vasculature during REM sleep, suggesting that the sympathetic outflow to the splanchnic organs and the brain may possibly be decreased during REM sleep, with the consequence that blood flow to the splanchnic organs and the brain increased (Cianci et al. 1991; Osborne, 1997; Yoshimoto et al. 2004). By contrast, muscle blood flow decreased during REM sleep (Baccelli et al. 1974; Miki et al. 2004). Miki et al. (2004) performed simultaneous measurements of common iliac blood flow and lumbar sympathetic nerve activity and showed that there was a significant (P < 0.05) inverse linear relationship between lumbar sympathetic nerve activity and iliac blood flow during the transition between non-rapid eye movement (NREM) and REM sleep; they further demonstrated that unilateral lumbar sympathectomy blunted the reduction in iliac blood flow induced by the onset of REM sleep. Consistent with the observation in rats, Baccelli et al. (1974) demonstrated in cats that REM sleep induced a long-lasting constriction of muscle blood vessels, which was abolished after sympathectomy. These data suggested that the increase in lumbar sympathetic nerve activity exerted a vasoconstrictor influence on the muscle vasculature. It is therefore likely that the diverse response in sympathetic nerve activity during REM sleep is responsible for vasodilatation in the kidney taking place concomitantly with vasoconstriction in the skeletal muscle.
Systemic arterial pressure initially remains either unchanged or increased during the transition between NREM and REM sleep in humans and rats (Somers et al. 1993; Miki et al. 2003a). This has been a puzzling feature because the onset of REM sleep results in reductions of renal sympathetic nerve activity, cardiac output and heart rate as well as vasodilatation in the splanchnic organs (Miller & Horvath, 1976; Zanchetti et al. 1982), which might serve to decrease systemic arterial pressure. Figure 1 provides evidence that systemic arterial pressure increased despite the decreased renal sympathetic nerve activity during REM sleep. One possible clue to solve this enigma might be related to the regional diversity of sympathetic nerve activity during REM sleep described above. If the lumbar sympathetic outflow going to the hindquarter skeletal muscle causes a decrease in the hindquarter muscle vascular conductance, and possibly a reduced skeletal muscle vascular conductance throughout the whole body, this may effectively balance the rise in the vascular conductance of the kidney and visceral organs as well as the decrease in cardiac output observed during REM sleep. Consequently, the overall balance between these two effects could result in the increase in systemic arterial pressure during REM sleep.
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There is now a body of evidence showing that a rise in physical activity causes increases in sympathetic outflows to both the kidney and skeletal muscle. Renal sympathetic nerve activity increased immediately after the onset of moving/exercise in rats (Miki et al. 2002, 2003b; Yoshimoto et al. 2003), rabbits (O'Hagan et al. 1993) and cats (Matsukawa et al. 1991). Hohimer & Smith (1979) demonstrated in the conscious baboon that 4 min of dynamic leg exercise decreased renal blood flow through the innervated kidney by 15% (P < 0.05) while renal blood flow through the surgically denervated kidney fell by only 1%. Yoshimoto et al. (2004) demonstrated in conscious rats that renal sympathetic nerve activity increased by 29% (P < 0.05) during voluntary movement that was accompanied by a significant reduction in renal blood flow by 7% (P < 0.05), which was abolished by renal denervation. Thus, the reduction in renal blood flow observed during moving/exercise seems to be attributable to the elevation in renal sympathetic nerve activity. If such an increase in sympathetic outflow occurs to all visceral beds then this would explain the consistent observation of a reduction of regional blood flow in the visceral organs observed during exercise (Rowell, 1986).
Muscle sympathetic nerve activity during exercise has been investigated extensively in man (Seals & Victor, 1991). However, measurement of sympathetic nerve activity to the contracting muscle is not possible, because even minimal motion of the limb under examination may dislodge the recording electrode. Although little is known of the response of the sympathetic nerve activity going to the actively contracting muscle, non-contracting muscle sympathetic nerve activity is consistently increased during exercise in humans (Seals & Victor, 1991). We have recently studied changes in lumbar sympathetic nerve activity in the rat, measured between L3 and L4 which contain fibres innervating mainly hindquarter skeletal muscle and skin, which increased immediately on the start of walking (authors' unpublished observation). Thus, there is a consensus that sympathetic nerve activity to the contracting muscle is increased in both human and rats.
Taking this information together, it is clear that exercise induces a simultaneous increase in sympathetic outflow to the kidney as well as skeletal muscle. Moreover, the magnitude of the changes in sympathetic outflow to both the kidney and skeletal muscle seems to be correlated with exercise intensity. It has been found in freely moving rats that renal sympathetic nerve activity increased progressively and linearly with an increase in the level of physical activity, which occurred during the transition from NREM sleep to quiet awake, moving and grooming states (Miki et al. 2003a). Muscle sympathetic nerve activity recorded from the non-contracting muscle in humans has also been shown to increase in proportion to the increase in exercise intensity (Saito et al. 1993). It has been consistently reported that systemic arterial pressure, heart rate and sympathetic nerve activity change in a unidirectional manner associated with an increase in the level of physical activity including both voluntary movement and exercise. For instance, a linear relationship between renal sympathetic nerve activity and systemic arterial pressure has been reported during the transition from NREM sleep to quiet awake, moving and grooming states in rats (Fig. 1; Miki et al. 2003a). It is therefore likely that an increase in physical activity over the activity range NREM sleep, to wakefulness and to exercise may exert a progressive and uniform activation of sympathetic outflow to the kidney and skeletal muscle.
In this review, we have considered the sympathetic nerve activity responses to sleep and exercise. In preliminary experiments, we have found that drinking and eating behaviour induced a different pattern of changes in renal and lumbar sympathetic outflow in rats (authors' unpublished observation). It will be of interest to study whether other behavioural states, for example sexual and social activity, involve differential changes in sympathetic outflows. It is highly possible that the central nervous system could generate state-specific patterns of activity involving differential changes in sympathetic outflows to relevant organs to organize whole body functions required for normal daily activity.
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Acknowledgements
We thank Dr E. J. Johns (Department of Physiology, University College Cork, Ireland) for critical reading of the manuscript.
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