REVIEW ARTICLE
Sports Medicine 13 (5): 303-319, 1992 0112-1642/92/0005-0303/$08.50/0 © Adis International Limited. All rights reserved. SP01132
Neural Influence on Cardiovascular and Endocrine Responses to Static Exercise in Humans Michael Kjaer and Niels H, Secher Departments of Internal Medicine TT A and Anaesthesia, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Contents 303 304 305 305 309 309
313 313 315 315 315 316
Summary
Summary I. Historical Perspective 2. Central and Reflex Neural Mechanisms 3. Onset of Static Exercise 4. Sustained Static Exercise 4.1 Cardiovascular Responses to Static Exercise 4.2 Endocrine Responses to Static Exercise 4.2.1 Catecholamines 4.2.2 Pituitary Hormones 4.2.3 Pancreatic Hormones 4.2.4 Other Responses 5. Practical and Clinical Implications
At the onset of exercise, signals from the central nervous system result in immediate vagal withdrawal and resulting increases in heart rate and arterial blood pressure. From the second heart beat peripheral nerve (reflex) influence from exercising muscle can be detected. With continued exertion, especially with large muscle groups, this influence becomes increasingly important. Sympathetic nerve signals to resting muscle can be influenced by the central nervous system, but are dominated by influence from 'metaboreceptors' in exercising muscle, while sympathetic nerve signals to skin are more influenced by the central nervous system. Cardiovascular responses to static contractions increase with the percentage of maximum contraction intensity as well as with the muscle mass involved. Plasma catecholamines rise in proportion to increases in cardiovascular variables and are influenced by a central nervous mechanism early in the contraction. Furthermore, during static contractions the increase in plasma adrenaline (epinephrine) is larger relative to that of noradrenaline than during dynamic exercise. Both catecholamine responses and the responses of pituitary hormones depend on the active muscle mass, but are small compared to those established during dynamic exercise. Experiments designed to enhance central command, resulting in increased cardiovascular and endocrine responses compared to control experiments and experiments in which an attenuation of peripheral nerve influence resulted in reduced changes in these variables during exercise, contrast with the notion that the 2 neural control mechanisms are redundant. Rather, the 2 neural influences on the autonomic nervous system work in concert in eliciting the responses manifest during static exercise.
304
Cardiovascular and hormonal responses to exercise increase with work intensity. In dynamic exercise the oxygen consumption of working muscle defines the activity and is met by an increase in cardiac output. During static exercise the intensity is determined by a certain muscle group (%MVC). This type of exercise is accompanied by increases in mean arterial blood pressure, heart rate and to a minor degree a rise in cardiac output and plasma concentrations of hormones and metabolites. Two mechanisms of neural control of circulation and metabolism are generally accepted. One is that exercise-induced changes are caused by signals arising in some central area of the brain that activates the motor cortex, the cardiovascular control areas in the medulla, and the endocrine centres. The other control mechanism is thought to be signals arising in the contracting skeletal muscles which reflexively activate cardiovascular control areas in the medulla or neuroendocrine centres (Johansen 1893; Mitchell 1985). Cardiovascular variables, plasma concentrations of hormones and metabolites and autonomic neural activity have been studied in situations where the central nervous and/or reflex influences are altered in order to understand regulation of the autonomic nervous system during static exercise. These manipulations have been used in order to define the role of 'feed-forward control', also called 'cortical irradiation' or 'central command' as opposed to the role played by 'feed-back control' arising from error signals in the working muscles ('the exercise pressor response' also called 'reflex control') in determining cardiovascular adaptations taking place during exercise (Mitchell 1985, 1990; Mitchell & Schmidt 1983; Mitchell et al. 1983; Rowell 1986; Rowell & O'leary 1990). More recently, this discussion has been extended to evaluate neural control of hormonal release during exercise (Galbo et al. 1987; Kjaer et al. 1987, 1989b). This scheme represents only a simplified model, disregarding independent influences from baroreceptors or changes in blood concentrations of metabolites (Galbo 1983; Ludbrook 1983; Rowell 1986). This review, nevertheless, is limited mainly
Sports Medicine 13 (5) 1992
to human experiments where the respective roles of feed-forward and neural feed-back control have been evaluated. It is pointed out that the role of the 2 neural control mechanisms are different at the onset of exercise and during continued exertion. Furthermore, it is argued that while the role of feed-forward control on cardiovascular responses can easily be demonstrated during static exercise, during dynamic exercise its role becomes apparent only after training involving a large muscle mass (Secher 1983a). Previously it has been argued that the 2 control mechanisms show redundancy in other words, that the normal responses to exercise represent a controlled level of activity, independent of the relative efficacy of the 2 main influences on the cardiovascular system. A central theme of this review is to demonstrate situations where enhancement or attenuation of the 2 neural pathways does not lead to normal responses, arguing the view that the 2 mechanisms are additive in establishing the adaptations taking place during exercise. With few data on control of hormonal regulation during static exercise, the review is dominated by studies indirectly demonstrating the origin of neural influences on cardiovascular variables in humans.
1. Historical Perspective Experiments to define neural control of circulation during exercise formed the foundation of exercise physiology and raised the questions currently being asked by investigators. These studies focused more on dynamic than on static exercise. One suggestion was that the increase in heart rate during exercise is related to the increase in body temperature (Mansfeld 1910). From experiments by Johansson (1893) and Aulo (1908, 1911) it was inferred that the heart rate response to exercise is of central nervous origin, as it could not be related to muscle metabolism, limb movement, the increase in ventilation and/or to a rise in body temperature. Furthermore, since the diastolic interval decreases more than systole during exercise, the heart rate response to exercise is dominated by va-
Neural Influence on Responses to Static Exercise
gal withdrawal. Krogh and Lindhard (1913) found the increase in heart rate in the first heart beat after the onset of dynamic exercise, indicating a neural and probably central mechanism. This notion was substantiated when they demonstrated a delay of I heart beat in the heart rate response to dynamic exercise induced by electrical stimulation (Krogh & Lindhard 1917). The influence of feed-forward control during dynamic exercise has also been addressed in experiments with partial neuromuscular blockade, making exercise more difficult, and thereby presumably enhancing the central nervous influence on the recorded cardiovascular, ventilatory and neuroendocrine parameters when the workload remains constant or is diminished. In such studies Ochwadt et al. (1959), Asmussen et al. (1965) and more recently Galbo et al. (1987) saw little or no effect on heart rate and blood pressure responses, while ventilation and catecholamine responses to dynamic exercise were enhanced. Conversely, peripheral neural influence on circulation has been attenuated by the use of regional anaesthesia (Fernandes et al. 1990; Freund et al. 1979; Strange et al. 1991). Another approach has been to compare exercise responses with those elicited after end of exercise, when blood has been trapped in the previously exercising extremity by way of an external arterial cuff (Alam & Smirk 1937, 1938; Asmussen et al 1943; Rowell et al. 1976). In these studies it is found that the cuff maintains heart rate and, more clearly, blood pressure elevated after end of exercise dependent on an intact afferent input from the muscles (Fernandes et al. 1990; Freund et al. 1979).
1. Central and Reflex Neural Mechanisms It has been possible to define neural pathways of importance for the exercise responses. Neural influence on circulation arising in muscles during exercise are confined to the group III and IV afferents from 'unencapsulated nerve endings' (Mitchell 1990). Although the role of the 2 types of afferents during exercise cannot be separated completely, the group III nerves appear to respond
305
mainly to mechanical events occuring in the muscle, reflecting an association with collagen structures. The group IV afferents are associated with blood and lymphatic vessels and respond to chemical change occuring within muscle during contraction, e.g. potassium levels, intramuscular pH and/or prostaglandins. However, the relative role of these stimuli and of other substances is far from clear. Iwamoto et al. (1989) has demonstrated that integration of neural influences from the working muscle during muscle contractions is located in the lateral reticular nucleus of the brain stem. The central neural mechanism of importance for cardiovascular responses to exercise may be located to the subthalamic locomotor region (Eldrige et al. 1985; Hajduczok et al. 1991; Waldrop et al. 1986). In addition, central neural mechanisms may also cause release of hormones and/or neurotransmittor substance. Electrical stimulation of the anteroventral region of the third ventricle causes release of adrenaline stored in sympathetic nerve terminals, and, in turn, vasodilation within skeletal muscle and vasoconstriction in splanchnic and renal vascular beds (Berecek & Brody 1982). Furthermore, release of hormones from endocrine glands, and in turn, fuel mobilisation from liver and adipose tissue is elicited by stimulation of the subthalamic locomotor region of both anaesthetised and decorticated cats (Vissing et al. I 989a,b).
3. Onset
0/ Static Exercise
In the first beat after the onset of static exercise, heart rate increases when the force applied is above 40 to 50% MVC (Secher 1985). At lower contraction intensities, heart rate either remains at or drops below resting levels (fig. I). The immediate increase in heart rate at the onset of both static and dynamic exercise is due to vagal withdrawal, as it is eliminated by atropine but not affected by t/-blockers (propranolol) [Freyschuss 1970; Hollander 1975a]. In attempts to define the relative roles of central vs peripheral neural factors for the cardiovascular responses to exercise, early studies have suggested that the increase in
306
Sports Medicine 13 (5) 1992
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Sports Medicine 13 (5): 303-319, 1992 0112-1642/92/0005-0303/$08.50/0 © Adis International Limited. All rights reserved. SP01132
Neural Influence on Cardiovascular and Endocrine Responses to Static Exercise in Humans Michael Kjaer and Niels H, Secher Departments of Internal Medicine TT A and Anaesthesia, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Contents 303 304 305 305 309 309
313 313 315 315 315 316
Summary
Summary I. Historical Perspective 2. Central and Reflex Neural Mechanisms 3. Onset of Static Exercise 4. Sustained Static Exercise 4.1 Cardiovascular Responses to Static Exercise 4.2 Endocrine Responses to Static Exercise 4.2.1 Catecholamines 4.2.2 Pituitary Hormones 4.2.3 Pancreatic Hormones 4.2.4 Other Responses 5. Practical and Clinical Implications
At the onset of exercise, signals from the central nervous system result in immediate vagal withdrawal and resulting increases in heart rate and arterial blood pressure. From the second heart beat peripheral nerve (reflex) influence from exercising muscle can be detected. With continued exertion, especially with large muscle groups, this influence becomes increasingly important. Sympathetic nerve signals to resting muscle can be influenced by the central nervous system, but are dominated by influence from 'metaboreceptors' in exercising muscle, while sympathetic nerve signals to skin are more influenced by the central nervous system. Cardiovascular responses to static contractions increase with the percentage of maximum contraction intensity as well as with the muscle mass involved. Plasma catecholamines rise in proportion to increases in cardiovascular variables and are influenced by a central nervous mechanism early in the contraction. Furthermore, during static contractions the increase in plasma adrenaline (epinephrine) is larger relative to that of noradrenaline than during dynamic exercise. Both catecholamine responses and the responses of pituitary hormones depend on the active muscle mass, but are small compared to those established during dynamic exercise. Experiments designed to enhance central command, resulting in increased cardiovascular and endocrine responses compared to control experiments and experiments in which an attenuation of peripheral nerve influence resulted in reduced changes in these variables during exercise, contrast with the notion that the 2 neural control mechanisms are redundant. Rather, the 2 neural influences on the autonomic nervous system work in concert in eliciting the responses manifest during static exercise.
304
Cardiovascular and hormonal responses to exercise increase with work intensity. In dynamic exercise the oxygen consumption of working muscle defines the activity and is met by an increase in cardiac output. During static exercise the intensity is determined by a certain muscle group (%MVC). This type of exercise is accompanied by increases in mean arterial blood pressure, heart rate and to a minor degree a rise in cardiac output and plasma concentrations of hormones and metabolites. Two mechanisms of neural control of circulation and metabolism are generally accepted. One is that exercise-induced changes are caused by signals arising in some central area of the brain that activates the motor cortex, the cardiovascular control areas in the medulla, and the endocrine centres. The other control mechanism is thought to be signals arising in the contracting skeletal muscles which reflexively activate cardiovascular control areas in the medulla or neuroendocrine centres (Johansen 1893; Mitchell 1985). Cardiovascular variables, plasma concentrations of hormones and metabolites and autonomic neural activity have been studied in situations where the central nervous and/or reflex influences are altered in order to understand regulation of the autonomic nervous system during static exercise. These manipulations have been used in order to define the role of 'feed-forward control', also called 'cortical irradiation' or 'central command' as opposed to the role played by 'feed-back control' arising from error signals in the working muscles ('the exercise pressor response' also called 'reflex control') in determining cardiovascular adaptations taking place during exercise (Mitchell 1985, 1990; Mitchell & Schmidt 1983; Mitchell et al. 1983; Rowell 1986; Rowell & O'leary 1990). More recently, this discussion has been extended to evaluate neural control of hormonal release during exercise (Galbo et al. 1987; Kjaer et al. 1987, 1989b). This scheme represents only a simplified model, disregarding independent influences from baroreceptors or changes in blood concentrations of metabolites (Galbo 1983; Ludbrook 1983; Rowell 1986). This review, nevertheless, is limited mainly
Sports Medicine 13 (5) 1992
to human experiments where the respective roles of feed-forward and neural feed-back control have been evaluated. It is pointed out that the role of the 2 neural control mechanisms are different at the onset of exercise and during continued exertion. Furthermore, it is argued that while the role of feed-forward control on cardiovascular responses can easily be demonstrated during static exercise, during dynamic exercise its role becomes apparent only after training involving a large muscle mass (Secher 1983a). Previously it has been argued that the 2 control mechanisms show redundancy in other words, that the normal responses to exercise represent a controlled level of activity, independent of the relative efficacy of the 2 main influences on the cardiovascular system. A central theme of this review is to demonstrate situations where enhancement or attenuation of the 2 neural pathways does not lead to normal responses, arguing the view that the 2 mechanisms are additive in establishing the adaptations taking place during exercise. With few data on control of hormonal regulation during static exercise, the review is dominated by studies indirectly demonstrating the origin of neural influences on cardiovascular variables in humans.
1. Historical Perspective Experiments to define neural control of circulation during exercise formed the foundation of exercise physiology and raised the questions currently being asked by investigators. These studies focused more on dynamic than on static exercise. One suggestion was that the increase in heart rate during exercise is related to the increase in body temperature (Mansfeld 1910). From experiments by Johansson (1893) and Aulo (1908, 1911) it was inferred that the heart rate response to exercise is of central nervous origin, as it could not be related to muscle metabolism, limb movement, the increase in ventilation and/or to a rise in body temperature. Furthermore, since the diastolic interval decreases more than systole during exercise, the heart rate response to exercise is dominated by va-
Neural Influence on Responses to Static Exercise
gal withdrawal. Krogh and Lindhard (1913) found the increase in heart rate in the first heart beat after the onset of dynamic exercise, indicating a neural and probably central mechanism. This notion was substantiated when they demonstrated a delay of I heart beat in the heart rate response to dynamic exercise induced by electrical stimulation (Krogh & Lindhard 1917). The influence of feed-forward control during dynamic exercise has also been addressed in experiments with partial neuromuscular blockade, making exercise more difficult, and thereby presumably enhancing the central nervous influence on the recorded cardiovascular, ventilatory and neuroendocrine parameters when the workload remains constant or is diminished. In such studies Ochwadt et al. (1959), Asmussen et al. (1965) and more recently Galbo et al. (1987) saw little or no effect on heart rate and blood pressure responses, while ventilation and catecholamine responses to dynamic exercise were enhanced. Conversely, peripheral neural influence on circulation has been attenuated by the use of regional anaesthesia (Fernandes et al. 1990; Freund et al. 1979; Strange et al. 1991). Another approach has been to compare exercise responses with those elicited after end of exercise, when blood has been trapped in the previously exercising extremity by way of an external arterial cuff (Alam & Smirk 1937, 1938; Asmussen et al 1943; Rowell et al. 1976). In these studies it is found that the cuff maintains heart rate and, more clearly, blood pressure elevated after end of exercise dependent on an intact afferent input from the muscles (Fernandes et al. 1990; Freund et al. 1979).
1. Central and Reflex Neural Mechanisms It has been possible to define neural pathways of importance for the exercise responses. Neural influence on circulation arising in muscles during exercise are confined to the group III and IV afferents from 'unencapsulated nerve endings' (Mitchell 1990). Although the role of the 2 types of afferents during exercise cannot be separated completely, the group III nerves appear to respond
305
mainly to mechanical events occuring in the muscle, reflecting an association with collagen structures. The group IV afferents are associated with blood and lymphatic vessels and respond to chemical change occuring within muscle during contraction, e.g. potassium levels, intramuscular pH and/or prostaglandins. However, the relative role of these stimuli and of other substances is far from clear. Iwamoto et al. (1989) has demonstrated that integration of neural influences from the working muscle during muscle contractions is located in the lateral reticular nucleus of the brain stem. The central neural mechanism of importance for cardiovascular responses to exercise may be located to the subthalamic locomotor region (Eldrige et al. 1985; Hajduczok et al. 1991; Waldrop et al. 1986). In addition, central neural mechanisms may also cause release of hormones and/or neurotransmittor substance. Electrical stimulation of the anteroventral region of the third ventricle causes release of adrenaline stored in sympathetic nerve terminals, and, in turn, vasodilation within skeletal muscle and vasoconstriction in splanchnic and renal vascular beds (Berecek & Brody 1982). Furthermore, release of hormones from endocrine glands, and in turn, fuel mobilisation from liver and adipose tissue is elicited by stimulation of the subthalamic locomotor region of both anaesthetised and decorticated cats (Vissing et al. I 989a,b).
3. Onset
0/ Static Exercise
In the first beat after the onset of static exercise, heart rate increases when the force applied is above 40 to 50% MVC (Secher 1985). At lower contraction intensities, heart rate either remains at or drops below resting levels (fig. I). The immediate increase in heart rate at the onset of both static and dynamic exercise is due to vagal withdrawal, as it is eliminated by atropine but not affected by t/-blockers (propranolol) [Freyschuss 1970; Hollander 1975a]. In attempts to define the relative roles of central vs peripheral neural factors for the cardiovascular responses to exercise, early studies have suggested that the increase in
306
Sports Medicine 13 (5) 1992
•
-8
•
-6
i
-4
•
~
C, c .S!
a:
ri:
-2
.£ Q)
Cl
••
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