The autonomic nervous system and the CVS

Question 1

What is the function of the autonomic nervous system?

Answer 1

• Important for regulating many physiological
functions:
– Heart rate, BP, body temperature… etc
(homeostasis)
– Co-ordinating the body’s response to exercise
and stress
– Largely outside voluntary control
• Exerts control over:
– smooth muscle (vascular and visceral)
– exocrine secretion
– rate and force of contraction in the heart

Question 2

What are the divisions of the autonomic nervous system, and what are the grounds for this division?

Answer 2

• The parasympathetic nervous system and the sympathetic nervous system
• This division is based on anatomical grounds
• Some text books include a third division the
enteric nervous system:
– Network of neurones surrounding GI tract
– Is normally controlled via sympathetic and
parasympathetic fibres

Question 3

What is the organisation (cellular level) of the ANS?

Answer 3

Two neurones in series, followed by target cell:
Preganglionic neurone ( cell body in central nervous system); postganglionic neurone (cell body in peripheral nervous system); target cell.

Question 4

Describe the organisation of the sympathetic nervous system.

Answer 4

•Thoracolumbar origin
• Preganglionic neurones arise from segments T1 to L2 (or L3). Preganglionic neurones are relatively short.
• Most synapse with postganglionic neurones (relatively long) in the paravertebral chain of ganglia
• Some synapse in a number of prevertebral ganglia:
– coeliac, superior mesenteric, inferior
mesenteric ganglia

Question 5

Describe the organisation of the parasympathetic nervous system.

Answer 5

• Craniosacral origin
• Preganglionic fibres (relatively long) travel in
cranial nerves (III (occularmotor), VII (facial), IX (glossopharangeal) & X (vagus)) or sacral outflow from S2-S4
• Synapse with neurones in ganglia close to the target tissue
• Short postganglionic neurones

Question 6

Describe the neuronal signalling between pre and postganglionic neurones in the ANS.

Answer 6

ACh released from preganglionic neurone activates nicotinic AChRs on postganglionic neurone, allowing influx of Na+ ions (some potassium efflux aldo, but at RMP not much; Na+ current more important).

Question 7

How is neurotransmission to effector cells mediated in the ANS?

Answer 7

• Postganglionic sympathetic neurones are usually noradrenergic (use noradrenaline (NA) as a transmitter), activating adrenoceptors
• Postganglionic parasympathetic neurones are usually cholinergic (have ACh as transmitter), activating muscarinic ACh receptors
• The exception is sympathetic innervation of the sweat glands:
– here postganglionic neurones release ACh which acts on muscarinic ACh receptors

Question 8

What is a chromaffin cell?

Answer 8

• Located in the adrenal medulla
• Act like specialised postganglionic sympathetic neurones
• Adrenal chromaffin cells release adrenaline which circulates in the blood stream

Question 9

What are adrenoceptors/adrenoreceptors?

Answer 9

• Activated by NA and adrenaline
• G protein-coupled receptors
– no integral ion channel
• Types and subtypes of adrenoreceptors
– α-adrenoreceptors: α1, α2
– β-adrenoreceptors: β1, β2
• Different tissues can have different subtypes
– Allows for diversity of action
– Selectivity of drug action

Question 10

Describe neurotransmission to target cells in the parasympathetic nervous system.

Answer 10

• Parasympathetic postganglionic neurones use ACh as a neurotransmitter
• ACh acts at muscarinic receptors on the effector cells
• G protein-coupled receptors (M1, M2 & M3)
• no integral ion channel

Question 11

What are the features of the autonomic nervous system?

Answer 11

• Regulates physiological functions
• Where parasympathetic and sympathetic divisions both innervate a tissue they often have opposite effects
• Sympathetic activity is increased under stress
• Parasympathetic system is more dominant under basal conditions
• Both work together to maintain balance

Question 12

Give an example of independent regulation of the sympathetic nervous system.

Answer 12

Sympathetic activity to the heart can be increased without increasing activity to GI tract
On some occasions (fight or flight) there can be a more co-ordinated sympathetic response

Question 13

How does the autonomic nervous system affect the cardiovascular system?

Answer 13

• The ANS controls
– heart rate
– force of contraction of heart
– peripheral resistance of blood vessels
• What the ANS does not do:
– The ANS does not initiate electrical activity
in the heart

Question 14

Describe the parasympathetic input to the heart.

Answer 14

• Preganglionic fibres - 10th (X) cranial nerve
VAGUS
• Synapse with postganglionic cells on epicardial surface or within walls of heart at SA and AV node
• Postganglionic cells release ACh
• Acts on M2-receptors
– decrease heart rate (-ve chronotropic effect)
– decrease AV node conduction velocity

Question 15

Describe sympathetic input to the heart.

Answer 15

• Postganglionic fibres from the sympathetic trunk
• Innervate SA node, AV node and myocardium
– Release noradrenaline
• Acts on β1 adrenoreceptors
– increases heart rate (+ve chrontropic effect)
– increases force of contraction (+ve inotropic
effect)

Question 16

Describe sympathetic input to pacemaker cells of the heart.

Answer 16

Sympathetic activity increases slope of pacemaker potential, making depolarisation and reaching of threshold quicker, thereby increasing heart rate.
Sympathetic effect mediated by β1 receptors
G-protein coupled receptors
Alpha (s) subunit increases cAMP, which directly activates HCN channels responsible for the pacemaker potential
This speeds up pacemaker potential

Question 17

Describe parasympathetic input to pacemaker cells of the heart.

Answer 17

Parasympathetic activity decreases slope of pacemaker potential, making depolarisation and reaching of threshold slower, thereby decreasing heart rate.
Parasympathetic effect mediated by M2 receptors
G-protein coupled receptors
Increase K+ conductance and decrease cAMP
Alpha(i) subunit decreases activity of HCN channels, beta- gamma subunit activates K+ channels, increasing K+ conductance, meaning that the cell takes longer to depolarise. Both of these effects slow down heart rate.

Question 18

How does noradrenaline increase the force of contraction?

Answer 18

• NA acting on β1 receptors in myocardium causes an increase in cAMP -> activates PKA
• Phosphorylation of Ca2+ channels
– increased Ca2+ entry during AP
• Increased uptake of Ca2+ in sarcoplasmic
reticulum
• Increased sensitivity of contractile machinery to Ca2+
• Increased force of contraction

Question 19

What are the effects of the autonomic nervous system on the vascular system?

Answer 19

• Most vessels receive sympathetic innervation
– exceptions
• Some specialised tissue e.g. erectile tissue have parasympathetic innervation
• Most arteries and veins have α1-adrenoreceptors
– Coronary and skeletal muscle vasculature also have β2-receptors

Question 20

What is vasomotor tone?

Answer 20

At rest, there is some sympathetic innervation of vasculature, which allows vasodilation or vasoconstriction when needed.
An increase in sympathetic output would cause vasoconstriction.
A decrease in sympathetic output would cause vasodilation.

Question 21

Which blood vessels contain B2-adrenoceptors, and what is the physiological relevance of this?

Answer 21

• Skeletal muscle, myocardium and liver
• Circulating adrenaline has a higher affinity for β2 adrenoceptors at physiological concentrations. This increases cAMP -> PKA -> opens potassium channels + inhibits MLCK, causing relaxation of smooth muscle.
• At higher pharmacological concentrations, α1-adrenoceptors are activated, causing vasoconstriction by increasing IP3 production. Increase in [Ca2+]i from stores and via influx of
extracellular Ca2+, leading to contraction of smooth muscle

Question 22

What is the role of local metabolites on vasodilation?

Answer 22

• Active tissue produces more metabolites
– e.g. adenosine, K+, H+, increase PCO2
• Local increases in metabolites have a strong
vasodilator effect
• More important for ensuring adequate perfusion of skeletal and coronary muscle than activation of β2-receptors

Question 23

Overall, how is the CVS regulated?

Answer 23

• Changes in the state of the system are
communicated to the brain via afferent nerves
– Baroreceptors (high pressure side of system)
– Atrial receptors (low pressure side of system)
• Alters activity of efferent nerves

Question 24

What are baroreceptors?

Answer 24

Nerve endings in the carotid sinus and aortic arch that are sensitive to stretch.
Increased arterial pressure stretches these
receptors.

Question 25

What is the baroreceptor reflex?

Answer 25

Increase in mean arterial pressure is detected by baroreceptors, and afferent pathways to the medulla are activated. Efferent pathways from the medulla mediate bradycardia and vasodilation to counteract increased mean arterial pressure.
The opposite can occur during a decrease in mean arterial pressure.

Question 26

What are the groups of drugs that affect the autonomic nervous system?

Answer 26

• Sympathomimetics
– α-adrenoceptor agonists
– β-adrenoceptor agonists
• Adrenoceptor antagonists
• Cholinergics
– Muscarinic agonists and antagonists

Question 27

Give uses and examples of sympathomimetics.

Answer 27

• Cardiovascular uses
– Administration of adrenaline to restore
function in cardiac arrest (causes vasoconstriction, helping to maintain BP and restore heart rate)
– β1 agonist (largely, but not completely, selective) - dobutamine may be given in
cardiogenic shock (pump failure)
– Adrenaline administered for anaphylactic shock (anaphylaxis- widespread vasodilation, causing a drop in BP)
• other uses
– β2 agonist – salbutamol for treatment of
asthma

Question 28

Give uses and examples of adrenoreceptor antagonists.

Answer 28

• α-adrenoreceptor antagonists:
– α1 antagonists e.g. prazosin
– anti-hypertensive agent
• Inhibits NA action on vascular smooth muscle α1-receptors, causing vasodilation
• β-adrenoreceptor anatgonists (given to patients after MI to reduce the work of the heart):
– propranolol
• non-selective β1/β2 antagonist
• slows heart rate and reduces force of contraction (β1) but also acts on bronchial smooth muscle (β2), causing bronchoconstriction (DON’T GIVE TO ASTHMATICS!!!)
– atenolol
• Selective β1 – less risk of bronchoconsriction

Question 29

Give uses and examples of cholinergic drugs.

Answer 29

• Muscarinic agonists
– e.g. pilocarpine
– used in treatment of gluacoma (reduces pressure in the eye)
• activates constrictor pupillae muscle
• Muscarinic antagonists
– e.g. atropine or tropicamide
– increases heart rate, bronchial dilation
– used to dilate pupils for examination of the eye