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Sympathetic Nervous System Physiology and Pathophysiology in Coping with the Environment

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Abstract

The sections in this article are:

1 Homeostatic Systems and Principles of Their Operation
1.1 Negative Feedback
1.2 Multiple Effectors and Effector Sharing
1.3 Resetting
2 Physiology of the Sympathetic Nervous System
2.1 Sympathetic Nerve Function
3 Sympathetic Nervous System Responses in Coping with the External and Internal Environment
3.1 Ontogeny
3.2 Changes in Sympathetic Function with Normal Aging
3.3 Circadian Rhythms
3.4 Orthostasis and Weightlessness
3.5 Exercise
3.6 Mental Challenge or Active Attention
3.7 Metabolism and Energy Balance
4 Sympathetic Function in Disease States
4.1 Sympathetic Neurocirculatory Dysfunction or Failure
4.2 Myocardial Ischemia and Infarction
4.3 Congestive Heart Failure
4.4 Other Conditions
5 Conclusion
Figure 1. Figure 1.

Some homeostatic systems. Items in boldface denote perturbations where the sympathetic nervous system (SNS) plays a role as an effector system.

Figure 2. Figure 2.

Schematic diagram showing processes of synthesis, release (R), neuronal reuptake (U1), extra‐neuronal uptake (U2), vesicular leakage (VL) and sequestration (VS), metabolism and turnover of NE in sympathetic nerve endings in relation to extraneuronal tissues and the bloodstream. Other abbreviations: TH = tyrosine hydroxylase; DBH = dopamine‐β‐hydroxylase; MAO = monoamine oxidase; COMT = catechol‐O‐methyltransferase; TYR = tyrosine; DOPA = 3, 4 = dihydroxyphenylalanine; DA = dopamine; NE = norepinephrine; DHPG = dihydroxyphenylglycol; NMN = normetanephrine; MHPG = methoxyhydroxyphenylglycol; DOPAC = dihydroxyphenylacetic acid.

Figure 3. Figure 3.

Schematic diagram showing the determinants of norepinephrine (NE) turnover and synthesis in sympathetic nerves during baseline conditions (upper panel) and during exercise (lower panel). Numbers with each arrow show the relative rates of each process. Norepinephrine turnover in sympathetic nerves is dependent on two inputs: (1) intraneuronal metabolism of NE leaking from storage vesicles or recaptured after release; and (2) escape from reuptake after release, with subsequent loss by extraneuronal uptake and metabolism or entry into the bloodstream. Because of to the large and constant impact on turnover of NE leakage from vesicular stores, a ten‐fold increase in norepinephrine release during exercise results in only a 3.2‐fold increase in NE turnover. Thus, NE synthesis need only increase by 3.2‐fold to maintain NE stores constant, despite a much larger ten‐fold increase in release.

Figure 4. Figure 4.

Thoracic positron emission tomographic scans after intravenous injection of 5 mCi of [13N]‐ammonia (NH3) and 1 mCi of 6‐[18F]Fluorodopamine (FDA) into a healthy volunteer (Normal); a patient with pure autonomic failure (PAF); a patient with the Shy‐Drager syndrome (SDS), which is a form of multiple system atrophy; and a patient with parkinsonism and sympathetic neurocirculatory failure (Park+). The pictures represent time‐averaged, nongated data. The right side of each picture corresponds to the left side of the subject.

Figure 5. Figure 5.

Diagram quantitatively illustrating the processes of synthesis, vesicular‐axoplasmic exchange, metabolism, release, neuronal and extraneuronal uptake, spillover, and turnover of norepinephrine for sympathetic nerves of the normal (left) and failing (right) human heart at rest. Numbers with each arrow represent the rates of each process in pmoles per minute. Abbreviations: U1, neuronal uptake; U2, extraneuronal uptake; TYR, tyrosine; DOPA, 3, 4‐dihydroxyphenylalanine; DOPAC, dihydroxy‐phenylacetic acid; DA, dopamine; NE, norepinephrine; DHPG, dihydroxyphenylglycol; DHPG‐SO4, dihydroxyphenylglycol‐sulfate; MHPG, methoxyhydroxyphenylglycol; NMN, normetanephrine; MAO, monoamine oxidase; COMT, catechol‐O‐methyltransferase.



Figure 1.

Some homeostatic systems. Items in boldface denote perturbations where the sympathetic nervous system (SNS) plays a role as an effector system.



Figure 2.

Schematic diagram showing processes of synthesis, release (R), neuronal reuptake (U1), extra‐neuronal uptake (U2), vesicular leakage (VL) and sequestration (VS), metabolism and turnover of NE in sympathetic nerve endings in relation to extraneuronal tissues and the bloodstream. Other abbreviations: TH = tyrosine hydroxylase; DBH = dopamine‐β‐hydroxylase; MAO = monoamine oxidase; COMT = catechol‐O‐methyltransferase; TYR = tyrosine; DOPA = 3, 4 = dihydroxyphenylalanine; DA = dopamine; NE = norepinephrine; DHPG = dihydroxyphenylglycol; NMN = normetanephrine; MHPG = methoxyhydroxyphenylglycol; DOPAC = dihydroxyphenylacetic acid.



Figure 3.

Schematic diagram showing the determinants of norepinephrine (NE) turnover and synthesis in sympathetic nerves during baseline conditions (upper panel) and during exercise (lower panel). Numbers with each arrow show the relative rates of each process. Norepinephrine turnover in sympathetic nerves is dependent on two inputs: (1) intraneuronal metabolism of NE leaking from storage vesicles or recaptured after release; and (2) escape from reuptake after release, with subsequent loss by extraneuronal uptake and metabolism or entry into the bloodstream. Because of to the large and constant impact on turnover of NE leakage from vesicular stores, a ten‐fold increase in norepinephrine release during exercise results in only a 3.2‐fold increase in NE turnover. Thus, NE synthesis need only increase by 3.2‐fold to maintain NE stores constant, despite a much larger ten‐fold increase in release.



Figure 4.

Thoracic positron emission tomographic scans after intravenous injection of 5 mCi of [13N]‐ammonia (NH3) and 1 mCi of 6‐[18F]Fluorodopamine (FDA) into a healthy volunteer (Normal); a patient with pure autonomic failure (PAF); a patient with the Shy‐Drager syndrome (SDS), which is a form of multiple system atrophy; and a patient with parkinsonism and sympathetic neurocirculatory failure (Park+). The pictures represent time‐averaged, nongated data. The right side of each picture corresponds to the left side of the subject.



Figure 5.

Diagram quantitatively illustrating the processes of synthesis, vesicular‐axoplasmic exchange, metabolism, release, neuronal and extraneuronal uptake, spillover, and turnover of norepinephrine for sympathetic nerves of the normal (left) and failing (right) human heart at rest. Numbers with each arrow represent the rates of each process in pmoles per minute. Abbreviations: U1, neuronal uptake; U2, extraneuronal uptake; TYR, tyrosine; DOPA, 3, 4‐dihydroxyphenylalanine; DOPAC, dihydroxy‐phenylacetic acid; DA, dopamine; NE, norepinephrine; DHPG, dihydroxyphenylglycol; DHPG‐SO4, dihydroxyphenylglycol‐sulfate; MHPG, methoxyhydroxyphenylglycol; NMN, normetanephrine; MAO, monoamine oxidase; COMT, catechol‐O‐methyltransferase.

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David S. Goldstein, Graeme Eisenhofer. Sympathetic Nervous System Physiology and Pathophysiology in Coping with the Environment. Compr Physiol 2011, Supplement 23: Handbook of Physiology, The Endocrine System, Coping with the Environment: Neural and Endocrine Mechanisms: 21-43. First published in print 2001. doi: 10.1002/cphy.cp070402