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Sympathetic Neural Activity to the Cardiovascular System: Integrator of Systemic Physiology and Interindividual Characteristics

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Abstract

The sympathetic nervous system is a ubiquitous, integrating controller of myriad physiological functions. In the present article, we review the physiology of sympathetic neural control of cardiovascular function with a focus on integrative mechanisms in humans. Direct measurement of sympathetic neural activity (SNA) in humans can be accomplished using microneurography, most commonly performed in the peroneal (fibular) nerve. In humans, muscle SNA (MSNA) is composed of vasoconstrictor fibers; its best‐recognized characteristic is its participation in transient, moment‐to‐moment control of arterial blood pressure via the arterial baroreflex. This property of MSNA contributes to its typical “bursting” pattern which is strongly linked to the cardiac cycle. Recent evidence suggests that sympathetic neural mechanisms and the baroreflex have important roles in the long term control of blood pressure as well. One of the striking characteristics of MSNA is its large interindividual variability. However, in young, normotensive humans, higher MSNA is not linked to higher blood pressure due to balancing influences of other cardiovascular variables. In men, an inverse relationship between MSNA and cardiac output is a major factor in this balance, whereas in women, beta‐adrenergic vasodilation offsets the vasoconstrictor/pressor effects of higher MSNA. As people get older (and in people with hypertension) higher MSNA is more likely to be linked to higher blood pressure. Skin SNA (SSNA) can also be measured in humans, although interpretation of SSNA signals is complicated by multiple types of neurons involved (vasoconstrictor, vasodilator, sudomotor and pilomotor). In addition to blood pressure regulation, the sympathetic nervous system contributes to cardiovascular regulation during numerous other reflexes, including those involved in exercise, thermoregulation, chemoreflex regulation, and responses to mental stress. © 2014 American Physiological Society. Compr Physiol 4:825‐850, 2014.

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Figure 1. Figure 1. Schematic summary of central neural mechanisms involved in baroreflex regulation of the heart and circulation. Baroreceptor afferent signals synapse at the nucleus tractus solitarii (NTS), after which glutaminergic excitatory fibers relay the cardiovascular information in two major directions: to the nucleus ambiguous (NA) and cardiac vagal motoneurones, and to the caudal ventrolateral medulla (CVLM). GABA‐ergic fibers from CVLM project to sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM) where they cause inhibition of subsequent efferent pre‐ and postganglionic sympathetic activities. Inhibitory neural connections are shown as dotted lines. Adapted from (103), with permission of Oxford University Press.
Figure 2. Figure 2. Inter‐individual variability of mean arterial pressure (MAP), cardiac output (CO) and total peripheral resistance (TPR) in young healthy subjects. Note that variability in CO and TPR is much greater than that of MAP. CV: coefficient of variation. From (36), with permission.
Figure 3. Figure 3. Relationships between MSNA and CO, MSNA and TPR and MSNA and MAP in young healthy men. MSNA was directly related to TPR, showing that it is a good index of whole body “net” vasoconstrictor tone in this group. The inverse relationship between MSNA and CO helps to balance the pressor effects of MSNA, contributing to the lack of relationship between MSNA and MAP. From (39), with permission.
Figure 4. Figure 4. Long‐term effects of afferent carotid sinus baroreceptor stimulation, showing prolonged decrease in mean arterial pressure for a period of 3 weeks. This effect was not seen in sino‐aortic denervated (SAD) animals. PBA: prolonged baroreflex activation. From (154), with permission.
Figure 5. Figure 5. Maintained responsiveness of MSNA to carotid baroreceptor stimulation (using the neck collar technique) during arm cycling exercise as compared to resting conditions. ECSP: estimated carotid sinus pressure. From (80), with permission.
Figure 6. Figure 6. Marked decrease in MSNA following exercise training in patients with congestive heart failure (CHF). Note lack of change in MSNA in CHF patients who did not exercise, and also lack of change in MSNA in control subjects following exercise training. From (206), with permission of Elsevier.
Figure 7. Figure 7. Relationships between MSNA responses to mental stress and MSNA responses to arousal or cold stress in a group of young healthy young men (see text for discussion). MSNA responses to mental stress were significantly related to MSNA responses to arousal, both when expressed as bursts/min and as bursts/100 heartbeats. There was no relationship between responses evoked by arousal and the cold test. From (58), with permission.


Figure 1. Schematic summary of central neural mechanisms involved in baroreflex regulation of the heart and circulation. Baroreceptor afferent signals synapse at the nucleus tractus solitarii (NTS), after which glutaminergic excitatory fibers relay the cardiovascular information in two major directions: to the nucleus ambiguous (NA) and cardiac vagal motoneurones, and to the caudal ventrolateral medulla (CVLM). GABA‐ergic fibers from CVLM project to sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM) where they cause inhibition of subsequent efferent pre‐ and postganglionic sympathetic activities. Inhibitory neural connections are shown as dotted lines. Adapted from (103), with permission of Oxford University Press.


Figure 2. Inter‐individual variability of mean arterial pressure (MAP), cardiac output (CO) and total peripheral resistance (TPR) in young healthy subjects. Note that variability in CO and TPR is much greater than that of MAP. CV: coefficient of variation. From (36), with permission.


Figure 3. Relationships between MSNA and CO, MSNA and TPR and MSNA and MAP in young healthy men. MSNA was directly related to TPR, showing that it is a good index of whole body “net” vasoconstrictor tone in this group. The inverse relationship between MSNA and CO helps to balance the pressor effects of MSNA, contributing to the lack of relationship between MSNA and MAP. From (39), with permission.


Figure 4. Long‐term effects of afferent carotid sinus baroreceptor stimulation, showing prolonged decrease in mean arterial pressure for a period of 3 weeks. This effect was not seen in sino‐aortic denervated (SAD) animals. PBA: prolonged baroreflex activation. From (154), with permission.


Figure 5. Maintained responsiveness of MSNA to carotid baroreceptor stimulation (using the neck collar technique) during arm cycling exercise as compared to resting conditions. ECSP: estimated carotid sinus pressure. From (80), with permission.


Figure 6. Marked decrease in MSNA following exercise training in patients with congestive heart failure (CHF). Note lack of change in MSNA in CHF patients who did not exercise, and also lack of change in MSNA in control subjects following exercise training. From (206), with permission of Elsevier.


Figure 7. Relationships between MSNA responses to mental stress and MSNA responses to arousal or cold stress in a group of young healthy young men (see text for discussion). MSNA responses to mental stress were significantly related to MSNA responses to arousal, both when expressed as bursts/min and as bursts/100 heartbeats. There was no relationship between responses evoked by arousal and the cold test. From (58), with permission.
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N. Charkoudian, B.G. Wallin. Sympathetic Neural Activity to the Cardiovascular System: Integrator of Systemic Physiology and Interindividual Characteristics. Compr Physiol 2014, 4: 827-850. doi: 10.1002/cphy.c130038