Sympathetic nervous system

Autonomic nervous system (ANS) consists of sympathetic nervous system (SNS) and Parasymphatetic nervous system (PSNS). Noradrenaline is the main neurotransmitter of the sympathetic nervous system.

Sympathetic system has a central role in the development of many cardiovascular diseases, such as essential hypertension and cardiac arrhythmias. Many drugs aim to reduce the activity of sympathetic nervous system, and PET has been used to study the effectiveness of these treatments.

Sympathetic nervous systems consists of two neuron types: pregangliotic, which originate from the thoracolumbar region of spinal cord, travel to ganglions next to the spine, connecting to postgangliotic neurons, which extend to the rest of the body. Pregangliotic neurons are cholinergic, and postgangliotic neurons are adrenergic, releasing noradrenaline in the peripheral nerve terminals. The adrenal medulla works as a distant ganglion, and the cromaffin cells in the medulla as postgangliotic neurons, except that, when activated, they release more adrenaline than noradrenaline. Adrenal medulla and SNS form the sympathoadrenal system, which interacts with thyroid hormones. Postgangliotic neurons that have their nerve endings in the kidney release dopamine with noradrenaline.

In the synthesis of noradrenaline the conversion of L-tyrosine to L-DOPA by tyrosine hydroxylase (TH) is the rate-limiting step, and TH is considered as a marker of sympathetic neurons.

The synaptic noradrenaline is metabolized by catechol-O-methyl-transferase (COMT) or monoamine oxidase (MAO), or deactivated by reuptake into the presynaptic neuron. After reuptake, noradrenaline is either moved into vesicles by vesicular monoamine transporter (VMAT) or metabolized by MAO in mitochondria.

Sympathetic activity and denervation

Sympathetic denervation can be detected using PET radiopharmaceuticals that are taken up by noradrenaline transporter (NAT/NET). Sympathetic activity can be assessed using radiopharmaceuticals that are transported into and stored in presynaptic vesicles, and released from them like noradrenaline.

Catecholamine synthesis rate can be estimated using [18F]FDOPA.

Cold pressor test (CPT)

Sympathetic activity increases during cold exposure, resulting in higher heart rate and blood pressure.

In the cold pressor test, heart rate and blood pressure is measured before and after hand is immersed into ice water for one minute. Cutaneous application of cold water increases sympathetic neural outflow, increasing arterial pressure and heart rate. Baroreflex returns the heart rate quickly to the normal level. Blood pressure change in CPT provides an approximate index of muscle sympathetic activity. CPT responses are exaggerated in hypertension prone individuals and increased in patients with ischemic heart disease, but impaired in patients with orthostatic hypotension caused by efferent sympathetic failure (Victor et al., 1987). Face cooling and handgrip exercise can also be used as sympathoexcitatory stimuli. CPT with myocardial perfusion imaging (MPI) can be used to assess coronary endothelial function (Schindler et al., 2004; Tuffier et al., 2016).


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Literature

Benarroch EE. Physiology and pathophysiology of the autonomic nervous system. Continuum (Minneap Minn) 2020; 26(1): 12-24. doi: 10.1212/CON.0000000000000817.

Gibbons CH. Basics of autonomic nervous system function. Handb Clin Neurol. 2019; 160: 407-418. doi: 10.1016/B978-0-444-64032-1.00027-8.

Imai J, Katagiri H. Regulation of systemic metabolism by the autonomic nervous system consisting of afferent and efferent innervation. Int Immunol. 2022; 34(2): 67-79. doi: 10.1093/intimm/dxab023.

Wehrwein EA, Orer HS, Barman SM. Overview of the anatomy, physiology, and pharmacology of the autonomic nervous system. Compr Physiol. 2016; 6(3): 1239-1278. doi: 10.1002/cphy.c150037.



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Updated at: 2023-01-17
Created at: 2017-10-07
Written by: Vesa Oikonen