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
• Postganglionic neurones = Acetylcholine and mAChR

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 (innervation and cellular mechanisms)

Answer 2

Parasympathetic innervation:

• Postganglionic fibres synapse onto cells on the epicardial surface or within the walls at SAN and AVN
• Release Ach which acts on M2 receptors (Gi coupled)
• Beta-gamma subunit increases K+ conductance and decreases cAMP
• This slows down the pacemaker potential (If current) due to less opening of HCN channels
• Decreases the heart rate
• Decreases AVN conduction velocity

Sympathetic innervation:

• Postganglionic fibres innervate SAN, AVN and myocardium
• Release noradrenaline which acts on B1 receptors mainly (Gs coupled)
• Increases cAMP
• This speeds up the pacemaker potential (If current) due to more opening of HCN channels
• Increases the heart rate
• Increases force of contraction

Question 3

Describe the mechanisms which control contraction of vascular smooth muscle cells (noradrenaline)

Answer 3

Only noradrenaline has an effect on the force of contraction!

• Noradrenaline acts on B1 AR (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 SR

This leads to increased contraction!

Question 4

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

Answer 4

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!

Question 5

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

Answer 5

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

• Nerve endings in the carotid sinus and the aortic arch are sensitive to stretch
• A drop in arterial blood pressure is detected by the baroreceptors and the signal is sent via afferent pathways to the medulla
• This reduces parasympathetic output which increases heart rate and increases sympathetic output which increases the heart rate and contractility and also causes vasoconstriction

Long term = neurohumoral response (i.e. days to years)
- Main aim is to control extracellular fluid (plasma) by controlling sodium excretion
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 6

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

Answer 6

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

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

Angiotensin II acts mainly on AT1 receptors to because different effects at different sites of the body to raise BP by arteriolar vasoconstriction etc.

Angiotensin II also causes aldosterone release from adrenal cortex which has its own effects to increase water retention

Question 7

Define the stages of hypertension

Answer 7

Stage 1 hypertension:

• Clinic blood pressure ranging from 140/90 mmHg to 159/99 mmHg
• ABPM ranging from 135/85 mmHg to 149/94 mmHg.

Stage 2 hypertension:

• Clinic blood pressure of 160/100 mmHg or higher but less than 180/120 mmHg
• ABPM of 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 120 mmHg or higher

Question 8

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

Answer 8

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

In the long term, hypertension can lead to coronary artery disease, myocardial infarction, heart failure, stroke, and renal failure.