The Sympathetic Nervous System and the Renin Angiotensin System

Question 1

Where do the parasympathetic and the sympathetic region originate from?

Answer 1

Parasympathetic comes from the craniosacral region.

Sympathetic comes from the thoracolumbar region

Question 2

Where the baroreceptors located?

Answer 2

Carotid sinus + aortic arch

Question 3

What neurotransmitter do all parasympathetic neurones release?

Answer 3

Acetylcholine

Question 4

What is the most common neurotransmitter released at the effector end of a sympathetic neurone and what are some exceptions?

Answer 4

Noradrenaline
Exceptions: the adrenal medulla acts as a specialised post-ganglionic neurone as the chromaffin cells produce mainly adrenaline (80%) and noradrenaline. Sympathetic neurons to sweat glands release acetylcholine.

Question 5

What are the two catecholamines?

Answer 5

Noradrenaline

Adrenaline

Question 6

where does synthesis of noradrenaline occur.

Answer 6

Occurs in the TERMINAL VARICOSITY: this is a small nodule at the end of the sympathetic nerve.

Question 7

Describe the two methods of uptake of catecholamines from the synaptic cleft and state the two enzymes involved in their breakdown.

Answer 7

They are either taken up into the presynaptic neuron that released them using Catechol-O Methyltransferase (COMT)

OR
into extraneuronal tissue.
Enzymes = Monoamine Oxidase (MAO)

Question 8

How are the adrenorecepors divided?

Answer 8

Alpha - excitatory on smooth muscle cells

Beta - relaxant on smooth muscle cells + stimulatory on heart

Question 9

what does it mean by stimulatory effect on the heart

Answer 9

it means that it increases the force of contraction (inotropic effect) and increases heart rate (chronotropic effect)

Question 10

Where are beta 1 receptors located?

Answer 10

Heart Muscle

GI tract

Question 11

What are the subdivision of BETA-receptors and where are they found?

Answer 11

Beta 1 receptors located on:

• cardiomycocytes
• smooth muscle of GI tract.

Beta 2:

• Vasculature
• Bronchi
• uterine smooth muscle

Beta 3:

• fat cells (brown fat)
• possibly on the smooth muscle of the GI tract

Question 12

Where are alpha 1 receptors located and what is their main function?

Answer 12

Post-synaptic membrane - they mediate VASOCONSTRICTION

Question 13

Where are alpha 2 receptors located and what is their function?

Answer 13

They are located on the presynaptic membrane and their activation by released transmitter causes NEGATIVE FEEDBACK inhibition of further transmitter release.
Some are post-synaptic on smooth muscle cells and cause VASOCONSTRICTION (like alpha 1 cells)

Question 14

What is the coupling of alpha-1 adrenoreceptors

Answer 14

via G proteins.

1. receptor is activated
2. causes the activation of phospholipase C.
3. PLC converts PIP2 to IP3 which leads to a release of calcium from intracellular stores.
4. an increase in intracellular calcium in a muscle cell causes CONTRACTION

so activation of these receptors increases calcium levels and causes contraction.

Question 15

What is coupling of beta adrenoreceptors and alpha 2 adrenoreceptors?

Answer 15

Beta receptors are coupled with adenylate cyclase which increases the levels of cAMP.

Question 16

How do the effects of cAMP on smooth muscle, platelets and cardiomyocytes vary in beta receptors?

Answer 16

in SMOOTH MUSCLE and PLATELETS= cAMP which is an inhibitor so it prevents activation, makes smooth muscle RELAX and prevents platelet activation.
in CARDIOMYOCYTES= increase cAMP, like calcium, activates the cell- this is unique to cardiomyocytes

Question 17

what are the effects in alpha 2 receptors

Answer 17

Alpha 2 receptors are also calcium releasing receptors but this is more to do with inhibition of adenylate cyclase

Question 18

what is anaphylaxis?

Answer 18

Is an extreme allergic reaction where you get release of vasodilators and bronchoconstriction.

Question 19

Which adrenoreceptors do noradrenaline and adrenaline act on?

Answer 19

Noradrenaline = a1 + a2 + b1
Adrenaline = ALL the adrenoreceptors

Question 20

State two synthetic compounds that can act on the adrenoreceptors and which adrenoreceptors do they act on?

Answer 20

Isoprenaline = b1 + b2 (pure beta agonist) 
Phenylephrine = a1

Question 21

What is the effect of a) noradrenaline, b) adrenaline and c) isoprenaline on systolic BP, diastolic BP, mean (To calculate a mean arterial pressure, double the diastolic blood pressure and add the sum to the systolic blood pressure. Then divide by 3) BP and heart rate?

Answer 21

Noradrenaline = increase, increase, increase, decrease 
Adrenaline = increase, decrease, increase, increase 
Isoprenaline = increase, decrease, same, increase

Question 22

what is the effect of noradrenaline?

Answer 22

Noradrenaline massively increases total peripheral resistance, therefore the blood pressure rises.
You may get Reflex Bradycardia, this occurs because of the baroreceptor loop: vasoconstriction causes an increase in blood pressure which increases the firing frequency of the baroreceptors leading to the deactivation of the sympathetic innervation of the heart and increased activity of the vagus nerve leading to a reduced heart.

Question 23

what is the effect of adrenaline?

Answer 23

Direct increase in heart rate.

Adrenaline has quite potent VASODILATOR which means that it decreases diastolic blood pressure.

Question 24

What is the effect of isoprenaline?

Answer 24

It is a pure BETA AGONIST. The effects of it are limited because it isn’t going to cause any vasoconstriction and hence resistance won’t change much.

Question 25

summarise the effects of noradrenaline, adrenaline, isoprenaline

Answer 25

``` Noradrenaline= reflex bradychardia adrenaline= direct increase in heart rate isoprenaline= more direct increase in heart rate ```

Question 26

What three elements regulate renin release?

Answer 26

Amount of sodium reaching the macula densa cells. The less sodium there is, the more renin will be released. Blood pressure in the pre-glomerular vessels. Depends on the pressure within the preglomerular vessels- the lower the blood pressure, the more renin is released. Sympathetic activity can increase renin release: the more beta receptors are activated, the more renin is released.

Question 27

Describe ways in which the renin-angiotensin system can be inhibited.

Answer 27

ACE inhibitors - prevent conversion of angiotensin I to angiotensin II Angiotensin II type I receptors (AT1) antagonists - prevent angiotensin II from exerting its effects

Question 28

What type of receptor is an Angiotensin II Type 1 (AT1) receptor and what does it work to do?

Answer 28

G protein coupled receptors (Gi and Gq) | -it works to increase BLOOD pressure.

Question 29

What is the RAPID pressor response of angiotensin II?

Answer 29

Direct vasoconstriction Enhanced action of peripheral noradrenaline Increased sympathetic discharge Release of catecholamines from adrenal medulla

Question 30

What is the SLOW pressor response of angiotensin II?

Answer 30

Happens over weeks or months Increased sodium reabsorption in proximal tubule Increased release of aldosterone Altered renal haemodynamics - renal vasoconstriction + enhanced noradrenaline effects in the kidney

Question 31

Describe the effects of angiotensin II on the heart.

Answer 31

Increased preload and afterload | Increased vascular wall tension

Question 32

Decribe the effects of non-heamodynamic effects of aldosterone?

Answer 32

- increased expression of proto-oncogenes - increased production of growth factors - increased synthesis of extracellular matrix proteins

Question 33

Why don't ACE inhibitors completely wipe out angiotensin II production?

Answer 33

There is another pathway that converts angiotensin I in to angiotensin II. This reaction is carried out by CHYMASES

Question 34

What is another effect of ACE inhibitors other than reducing angiotensin II?

Answer 34

Reduce the breakdown of bradykininso more bradykinin is left.

Question 35

What effect do angiotensin II type 1 receptor antagonists have?

Answer 35

Selectively blocks the effects of angiotensin II | It has NO effects on the bradykinin system because ACE is working perfectly fine

Question 36

What is the effect of angiotensin II type 1 receptor antagonist

Answer 36

you can get angioodema(Angioedema affects the deeper layers, including the dermis, subcutaneous tissue, the mucosa, and submucosal tissues)

Question 37

What are two main stimuli for aldosterone release?

Answer 37

Angiotensin II | Increased Potassium

Question 38

What are some harmful effects of aldosterone release?

Answer 38

``` Hypertension -------> Heart Failure Primary Hyperaldosteronism (associated with benign tumours of the adrenal cortex) = HYPERTENSION + no oedema Secondary Hyperaldosteronism (excessive response of the body in heart failure and liver failure) = Low/Normal blood pressure + SEVERE OEDEMA ```

Question 39

What is a potent stimulus for the sympatho-adrenal and renin-angiotensin systems?

Answer 39

FLUID LOSS (e.g. severe haemorrhage)

Question 40

What is primary hyperaldosteronism and secondary hyperaldosteronism?

Answer 40

Primary hyperaldosteronism: associated with benign tumours of the adrenal cortex- this is associated with hypertension. Secondary hyperaldosteronism: excessive response of the body in heart failure and liver failure- the phenotype is completely different. Primary= high blood pressure + NO oedema Secondary= low/normal blood pressure + LOTS of oedema.