Session 5 ILOs - Autonomic Nervous System, Control of Blood Pressure and Hypertension

Question 1

Detail the neurotransmitters and receptors involved in the autonomic nervous system

Answer 1

2 branches of the autonomic nervous system: parasympathetic nervous system and the sympathetic nervous system

Parasympathetic nervous system:

• Preganglionic neurones = Acetylcholine and nAChR (nicotinic acetylcholine receptor)
• Postganglionic neurones = Acetylcholine and mAChR (muscarinic acetylcholine receptor)

Sympathetic nervous system

• Preganglionic neurones = Acetylcholine and nAChR
• Postganglionic neurones = Noradrenaline and adrenoceptors (two classes: alpha and beta)

QISS (SNS) QIQ (PNS)

Question 2

Explain the mechanisms by which the autonomic nervous system controls heart rate and force of contraction in the normal heart (FOC is covered in detail on another flashcard)

Answer 2

Parasympathetic innervation:

• Preganglionic fibres that travel in the vagus nerve synapse with postganglionic cells on the epicardial surface or within the walls of the heart, predominantly at SAN and AVN
• post ganglionic cells release Ach which acts on M2 receptors (Gi coupled)
• Beta-gamma subunit increases K+ conductance
• You get a decrease cAMP
• This slows down the pacemaker potential (If current) due to less opening of HCN channels
• Decreases the heart rate (negative chonotropic effect)
• Decreases AVN conduction velocity

Sympathetic innervation:
- Postganglionic fibres come from the sympathetic trunk and innervate SAN, AVN and myocardium
- Postganglionic cells release noradrenaline which mainly acts on B1 adrenoreceptors (Gs coupled)
- Increases cAMP
- This speeds up the pacemaker potential (If current) due to more opening of HCN channels
- Increases the heart rate (positive chronotropic effect)
(- Increases force of contraction (positive inotropic effect)) - Next flashcard

Question 3

Describe how noradrenaline increases force of contraction in the heart

Answer 3

Only noradrenaline has an effect on the force of contraction!

• Noradrenaline acts on Beta1 Adrenoreceptors (Gs coupled) which causes an increase in cAMP
• cAMP activates protein kinase A
• Protein kinase A causes phosphorylation of calcium channels so more calcium enters the cell during plateau of action potential
• Protein kinase A also causes phosphorylation of phospholamban which causes more calcium uptake into Sarcoplasmic Reticulum

This leads to increased force of contraction! (positive inotropic effect)

Question 4

Define the stages of hypertension

Answer 4

Stage 1 hypertension:

• Clinic blood pressure of greater than or equal to 140/90 mmHg
• Home blood pressure of 135/85 mmHg

Stage 2 hypertension:

• Clinic blood pressure of greater than or equal to 160/100 mmHg
• Home blood pressure of greater or equal 150/95 mmHg or higher

Stage 3 or severe hypertension:
- Clinic systolic blood pressure of 180 mmHg or higher or clinic diastolic blood pressure of 110 mmHg or higher

Question 5

Explain the impact of hypertension on organs and tissues in the body

Answer 5

Hypertension can damage endothelial cells, producing a number of proliferative responses, including arteriosclerosis.

In the long term, hypertension can lead to heart failure, myocardial ischaemia, myocardial infarction, retinopathy, cerebrovascular disease stroke, aneurism nephrosclerosis and renal failure.

Question 6

Describe the mechanisms which control contraction of vascular smooth muscle cells

Answer 6

• Noradrenaline Activating β2 adrenoreceptors (which are G- Alpha S coupled) causes vasodilation
– Increases cAMP → which activates PKA (protein kinase A) → opens potassium channels + inhibits MLCK (Myosin light-chain kinase ) → relaxation of smooth muscle

• Activating α1 adrenoreceptors (which are G-Alpha Q coupled) causes vasoconstriction
– Stimulates IP3 production
– The IP3 acts on IP3 receptors to cause
– A release of [Ca2+] from intracellular stores → THE CALCIUM IONS BIND TO CALMODULIN TO INITIATE CONTRACTION = contraction of smooth muscle

Question 7

Explain how blood pressure is controlled in the short and longer term

Answer 7

Short term = baroreceptors (i.e. seconds to minutes)

• Baroreceptors are found in carotid sinus and aortic arch
• They adjust parasympathetic and sympathetic inputs to the heart to alter cardiac output
• They also adjust sympathetic inputs into peripheral resistance vessels to alter TPR

Long term = neurohumoral response (i.e. days to years)
- Main aim is to control sodium balance and thus extracellular fluid volume
4 main pathways acting in parallel:
1. Renin-angiotensin-aldosterone system
2. Sympathetic nervous system
3. Antidiuretic hormone (ADH)
4. Atrial natriuretic peptide (ANP)

Question 8

Describe the role of the renin-angiotensin-aldosterone system in maintain blood pressure

Answer 8

• The RAAS gets activated when BP or BV drops, so it aims to increase them

Renin is released from granular cells in the juxtaglomerulus apparatus - trigged by:
- Reduced NaCl delivery to distal convoluted tubule
- Reduced perfusion pressure in kidneys
- Sympathetic stimulation of JGA - juxtaglomerulus apparatus
(Indicating low BP)

Renin accelerates the conversion of angiotensinogen to angiotensin I and then ACE - angiotensin converting enzyme - converts angiotensin I to angiotensin II

Angiotensin II acts on angiotensin receptor 1 and 2 (mainly on AT1 receptors) to cause effects at 5 different sites :

1) Arterioles - vasoconstriction
2) Kidneys - Stimulates sodium reabsorption at kidney
3) Sympathetic nervous system - increased release of noradrenaline
4) Hypothalamus - increases thirst sensation to increase ADH release
5) Adrenal cortex - stimulates release of Aldosterone

Aldosterone:

• acts on principal cells of collecting ducts
• stimulates Na+ and therefore water reabsorption
• activates apical Na+ channel and apical K+ channel
• also increases basolateral Na+ extrusion via Na/K/ATPase

(all of these are designed to increase sodium and thus water reabsorption so the volume of fluid in the blood changes and bp can be altered)

• Bradykinin is a vasodilator
• ACE also helps to break down bradykinin into peptide fragments
• So when ACE inhibitors are used to treat heart conditions like hypertension, they prevent the breakdown of bradykinin. This can cause a dry cough.

Question 9

Describe the baroreceptor reflex

Answer 9

1) Baroreceptors are stretch receptors located in the aortic arch and carotid sinus
2) Increased arterial blood pressure stretches these receptors more
3) Decreased arterial blood pressure stretches these receptors less
4) When there is high BP, the baroreceptor nerve endings have an increased stretch
5) This fires action potentials towards medullary control centre of the brain stem
6) This coordination centre then sends messages to the heart and blood vessels to decrease cardiac output and decrease constriction in the effector vessels
7) Causes bradycardia and vasodilation, in order to reduce BP

Question 10

Explain the role of the autonomic nervous system in controlling peripheral resistance

Answer 10

There is a level of tone of the blood vessel at rest due to sympathetic output which acts on the a1 AR (Gq coupled) in smooth muscle cells (release of IP3) causes contraction.

This means that vasodilation is able to occur by altering the sympathetic innervation.

• By increasing sympathetic output, vasoconstriction occurs
• By decreasing sympathetic output, vasodilation occurs

Some blood vessels however have b2 AR (Gs coupled) which are activated by adrenaline in addition to the a1 AR

• Adrenaline can bind to the b2 AR at low levels to because vasodilation
• However at higher levels Adrenaline can also bind to the a1 AR to cause vasoconstriction!