Sympathetic control of the cardiovascular system

Dr Ian Edwards

i.edwards@ucl.ac.uk
Learning Objectives

• Understand the general anatomical organisation of the sympathetic

nervous system

• Understand the role of the sympathetic nervous system in the reflex

control of heart rate and blood pressure

• Show experimental evidence for CNS regions influencing sympathetic

outflow
Autonomic Nervous System
Sympathetic innervation of the heart

Eldredge, LC., et al. (2008) Development 135: 2949-57

Sympathetic innervation of the heart
Sympathetic control of blood vessels
Sympathetic control of blood vessels

Adr Adr
Sympathetic ganglia -
pre and post ganglionic neurones

Eldredge, LC., et al. (2008) Development 135: 2949-57

Sympathetic ganglia -
pre and post ganglionic neurones
Sympathetic ganglia -
pre and post ganglionic neurones

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displayed.

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Sympathetic ganglia -
pre and post ganglionic neurones

C8 T1
T2

Strack, AM., & Loewy, AD. (1990) J Neurosci 10(7): 2139-47

Sympathetic innervation of the adrenal glands
Sympathetic preganglionic neurones
Reflex control of the sympathetic nervous system

• Baroreflex – valsalva

• Metaboreflex
Valsalva Manoeuver
Increased Decreased Blood Sympathetic
intrathoracic venous pressure drive
pressure return drops increases

HR Intrathoracic Venous BP and HR

increases to pressure return increase
try to fix BP released increases more

Sympathetic Everything
Baroreflex BP and HR
drive back to
triggered fall
removed normal
Valsalva Manoeuvre
Metaboreflex

Static Build up of Blood

exercise ischaemic pressure
performed metabolites increases
Metaboreflex
NA ?

Sympathetic Sympathetic
ACh
postganglionic preganglionic
NA neurones neurones
Part 2
Sympathetic preganglionic neurones

Glutamate Glycine
GABA

Angiotensin II Vasopressin

5-HT
Substance P

Noradrenaline

Llewellyn-Smith, IJ. (2009) J Chem Neuroanat 38(3): 231-9

Spinal cord interneurones

-
CAA
IML
Spinal cord interneurones

Deuchars, SA., et al. (2005) J Neurosci 25: 1063-70

Spinal cord interneurones

Deuchars, SA., et al. (2005) J Neurosci 25: 1063-70

Rostral ventrolateral medulla

RVLM
+
IML
Rostral ventrolateral medulla

Abbott, SB., et al. (2009) J Physiol 587(23): 5613-31

Channelrhodopsin 2 (ChR2)
Na
+

Na
+
Rostral ventrolateral medulla

Abbott, SB., et al. (2009) J Physiol 587(23): 5613-31

Raphe nuclei

Raphe

+
IML
Raphe nuclei

Salo, LM., et al. (2009) Am J Physiol Heart Circ Physiol 296(2): H318-24
Nucleus of the solitary tract

-
NTS
RVLM

+
CVLM

IML
The working heart brainstem preparation
Nucleus of the solitary tract

Simms, AE., et al. (2006) J Physiol 575:727-38

Part 3
Periaqueductal grey

PAG

Raphe
+

+
IML
Periaqueductal grey

Green, AL., & Paterson, DJ. (2008) Exp Physiol 93:1022-28

Periaqueductal grey

Green, AL., & Paterson, DJ. (2008) Exp Physiol 93:1022-28

Kidneys and blood pressure
Sympathetic control of the kidneys

Guyenet, PG. (2006) Nat Rev Neurosci 7(5): 335-46

Paraventricular nucleus

PVN

RVLM

IML
Paraventricular nucleus

Sriramula., et al. (2011) Cardiovasc Res 92(3): 401-8

Paraventricular nucleus

Sriramula., et al. (2011) Cardiovasc Res 92(3): 401-8

Paraventricular nucleus

Sriramula., et al. (2011) Cardiovasc Res 92(3): 401-8

Cerebellum
Cerebellum

Tsobota., et al. (2012) Neuroscience 201: 137-44

Summary
High BP

NTS CVLM RVLM

Spinal
interneurones

Posture? Heart
SPN
Dietary Sodium PVN SPGN
Spinal cord
Blood Vessels

PAG Raphe

Pain/fear
References
Abbott, SB., et al. (2009) J Physiol 587(23): 5613-31
Photostimulation of channelrhodopsin-2 expressing ventrolateral medullary
neurons increases sympathetic nerve activity and blood pressure in rats.
Deuchars, SA., et al. (2005) J Neurosci 25: 1063-70
GABAergic neurons in the central region of the spinal cord: a novel substrate
for sympathetic inhibition.
Eldredge, LC., et al. (2008) Development 135: 2949-57
Abnormal sympathetic nervous system development and physiological
dysautonomia in Egr3-deficient mice.
Green, AL., & Paterson, DJ. (2008) Exp Physiol 93:1022-28
Identification of neurocircuitry controlling cardiovascular function in humans
using functional neurosurgery: implications for exercise control.
Guyenet, PG. (2006) Nat Rev Neurosci 7(5): 335-46
The sympathetic control of blood pressure.
References
Llewellyn-Smith, IJ. (2009) J Chem Neuroanat 38(3): 231-9
Anatomy of synaptic circuits controlling the activity of sympathetic
preganglionic neurons
Salo, LM., et al. (2009) Am J Physiol Heart Circ Physiol 296(2): H318-24
Control of cardiac rate, contractility, and atrioventricular conduction by medullary
raphe neurons in anesthetized rats.
Simms, AE., et al. (2006) J Physiol 575:727-38
Disinhibition of the cardiac limb of the arterial baroreflex in rat: a role for
metabotropic glutamate receptors in the nucleus tractus solitarii.
Sriramula., et al. (2011) Cardiovasc Res 92(3): 401-8
ACE2 overexpression in the paraventricular nucleus attenuates angiotensin II
-induced hypertension.
Strack, AM., & Loewy, AD. (1990) J Neurosci 10(7): 2139-47
Pseudorabies virus: a highly specific transneuronal cell body marker in the
sympathetic nervous system.
Tsubota, T., et al (2012) Neuroscience 210: 137-44 Optogenetic inhibition of
Purkinje cell activity reveals cerebellar control of blood pressure during postural
alterations in anesthetized rats.