L10: Autonomic control of CVS

Question 1

What is the ANS important for?

Answer 1

Regulating physiological functions
HR, BP, Body temperature, coordinating body’s response to exercise and stress
Control over–> smooth muscle, exocrine secretion and rate and force of contraction of the heart
Maintain balance

Question 2

What are the divisions of the ANS?

Answer 2

Sympathetic--> fight or flight
--> thoracolumbar outflow
--> tissue can be independently regulated or it can be a more generalised 
Parasympathetic--> rest or digest
--> craniosacral outflow

Question 3

What is the arrangement of the pre- and post ganglionic fibres in the sympathetic and parasympathetic system?

Answer 3

Sympathetic
--> Short pre
--> Long post
--> ganglia in sympathetic chain 
Para-
--> Long pre
--> Short post
--> Ganglia in or close to target organ

Question 4

What affect does the sympathetic and parasympathetic nervous system have on the pupil of the eye? What are the main receptors involved?

Answer 4

Sympathetic–> Dilation –> constriction of radial eye muscles–> need to be able to see danger
–> α1
Parasympathetic –> Constriction–> contracts sphincter muscles
–> Muscarinic - M3

Question 5

What affect does the sympathetic and parasympathetic nervous system have on the lung? What are the main receptors involved?

Answer 5

Sympathetic–> bronchiodilation
–> β2
Parasympathetic–> bronchochonstriction
–> M3

Question 6

What affect does the sympathetic and parasympathetic nervous system have on the heart? What are the main receptors involved?

Answer 6

Sympathetic–> ↑HR and force of contraction (+ve Chrontrophy)
–> β1
Parasympathetic–> ↓ HR
–> M2

Question 7

What affect does the sympathetic and parasympathetic nervous system have on the sweat glands? What are the main receptors involved?

Answer 7

Sympathetic–> increase sweat production –> keep cool
–> localised secretion–> α1
–> generalised secretion –> M3
Parasympathetic–> no effect

Question 8

What role does the ANS play in the cardiovascular system?

Answer 8

Control HR, force of contraction and peripheral resistance of vasculature

Question 9

What happens if you de-innervate the heart?

Answer 9

Heart will still beat
ANS does not initate the electrical activity
Beats at faster rate–> normally under control of vagus nerve

Question 10

What is the parasympathetic input to the heart?

Answer 10

Via vagus (X) nerve–> synapse on postganglionic cells in the SA and AV node–> Post- ACh onto receptors
M2 receptors
–> Decrease HR
–> Decrease AV node conduction velocity

Question 11

What is the sympathetic input to the heart?

Answer 11

Preganglionic–> sympathetic chain–> Post- NA onto receptors
Innervate SA, AV node and myocardium
β1 receptors
–> Increase HR
–> Increase force of contraction (+ve chronotrophic effect)

Question 12

What do we mean by the pacemaker of the heart?

Answer 12

The Sinoatrial node controls the heart rate–> rhythm

Question 13

How does the pacemaker of the heart work?

Answer 13

Slow depolarising pacemaker potential–> funny current (If)–> slow inward current of Na+ ions (HCN channels)
Hits threshold–> fast Ca2+ channels open–> Ca2+ influx
Peak
Closing of Ca2+ channels opening of K+ channels–> repolarisation

Question 14

What are HCN channels?

Answer 14

Hyperpolarisation-activated Cyclic Nucleotide gated channels

Question 15

How does the sympathetic system effect the pacemaker potential of the heart?

Answer 15

Speeds up pacemaker potential
Increases the slope to threshold
Mediated by NA on β1 receptors–> ↑cAMP (acts on HCN channels)

Question 16

How does the parasympathetic system effect the pacemaker potential?

Answer 16

Slows down the pacemaker potential
Decrease the slope
Vagal nerve
Mediated by ACh on M2 receptors–>GPCR–> Gi –> ↑K+ conductance and decrease cAMP (reduced HCN activity)

Question 17

How does NA increase the force of contraction of heart?

Answer 17

β1 receptors--> GPCR
↑ cAMP--> ↑ PKA
-Phosphorylation of Ca2+ channels--> ↑Ca2+ entry during plateau phase of cardiomyocyte AP--> prolonges depolarisation
-Increase Ca2+ uptake in SR
Increase force of contraction

Question 18

How does the ANS affect the vasculature?

Answer 18

Mostly sympathetic innervation (some exceptions -erectile tissue)
α1 receptors
Coronary, liver and Skeletal Muscle vasculature also have β2 receptors

Question 19

How is vasculature regulated?

Answer 19

Vasomotor tone–> normal basal level
↑NA acts on α1 receptors–> vasoconstriction
↓NA less activation of α1 receptors–> vasodilation

Question 20

What is the effect of having α1 and β2 receptors in vasculature?

Answer 20

NA controls muscle vasculature without fight or flight (sympathetic input)
Adrenaline released from adrenal glands
–> Low levels (physiological concn) acts on β2 receptors–> vasodilation
–> higher binding affinity
–> High levels also acts on α1 receptors–> vasoconstriction (fight or flight ↑ adrenaline= vasoconstriction)

(b2 on skeletal muscle, myocardium and liver)

Question 21

What is the specific mechanism behind effect of B2 and a1 receptors in vascular smooth muscle?

Answer 21

• Adrenaline–> β2 –> αs subunit–> AC–> ↑cAMP–> PKA–> Open K+ channels and inhibit MLCK–> Vasodilation
• Adrenaline–> α1 –> αq subunit–> PC–> PIP2–> IP3 and DAG–> IP3 ↑Ca2+–> activates MLCK–> phosphorylates myosin light chain = activation (contraction)–> Also DAG –> PKC–> inhibit MLCP –> Vasoconstriction

Question 22

What is the most important thing for dilating blood vessels?

Answer 22

Local metabolites produced by active tissue (adenosine, potassium, H+ (pH change), CO2)
More important for ensureing adequate perfusion of skeletal and coronary muscle than activation of β2 receptors

Question 23

How does the brain know whether to vasoconstrict or vasodilate blood vessels?

Answer 23

Baroreceptors –> arch of aorta and carotid sinus–> high pressure system
Atrial receptors –> low pressure system

Question 24

How do the baroreceptors detect changes in blood pressure?

Answer 24

Stretch receptors
Increase pressure–> stretches baroreceptors (glossopharyngeal in CS, vagus in AA) –> Increase AP firing to brain
Decreases pressure–> less stretch –> decrease AP firing to brain

Question 25

What is the pathway for changing blood pressure?

Answer 25

↑ arterial blood pressure –> Baroreceptors detect stretch–> ↑ AP to medulla –> Efferent pathway –> ↓ HR, CO and vasodilate vessels –> ↓ arterial pressure

↓ arterial blood pressure –> Baroreceptors detect decreased stretch–> ↓ AP to medulla –> Efferent pathway –> ↑ HR, CO and vasoconstriction of vessels –> ↓ arterial pressure

Check lecture note slide 26

Question 26

What is the problem with prolonged high blood pressure?

Answer 26

Baroreceptors re-set to higher level

Elevated BP no longer stretched baroreceptors so no AP fired

Question 27

What drugs can act on the ANS?

Answer 27

Sympathomimetics–> Adrenoreceptor agonists
Adrenoreceptor antagonists
Cholinergics–> Muscarinic agonists and antagonists

Question 28

What are the uses of sympathomimetics?

Answer 28

Mimic agonists
α1–> pharmacological dose of adrenaline
–> cardiac arrest–> Vasoconstriction of BV increase blood flow to heart
–> Anaphylactic shock–> Overcome effects of β2 receptors (vasculature) activating α1 –> vasoconstriction

β1–> Dobutamine–> cardiogenic shock (heart can’t pump enough blood to meet needs)–> increases force of contraction in the heart and heart rate (without tachycardia)

β2–> Salbutamol–> Asthma–> Receptors in the lung causes bronchodilation

Question 29

What is the use of adrenoreceptor antagonists?

Answer 29

Prazosin–> a1 adrenoreceptor antagonist–> vasodilation of vasculature

Propanolol–> b1/b2 non selective antagonist

• b1–> decrease heart rate, reduce force of contraction
• b2–> bronchoconstriction

Atenolol–> B1 selective
-decrease HR and force of contraction without affecting lungs

CONFUSING EXPLAINATION
α adrenoreceptor antagonists–> inhibit NA on α1–> vasodilation e.g. prazosin antihypertensive drug

β adrenoreceptor antagonists–>

• -> Propranolol–> non selective β1/β2 antagonist–> β1 slows heart rate, β2 bronchoconstriction
• -> atenolol–> selective β1 (cardio-selective)–> slows HR less risk of bronchoconstriction

Question 30

What is the use of cholinergics?

Answer 30

Muscarinic agonist –>
–> Pilocarpine –> treatment of gluacoma–> activates constrictor pupillae muscles (M3)
Muscarinic antagonists
–> Atropine and tropicamide
–> increase HR and bronchial dilation (M2 + M3)
–> used to dilate pupils for the eye (M3)