08 Sympathetic Nervous System and Renin Angiotensin System

Question 1

Describe the processes of the biochemical synthesis of noradrenaline

Answer 1

Tyrosine -> DOPA (by tyrosine hydroxylase)
DOPA -> dopamine (by DOPA decarboxylase)
Dopamine -> noradrenaline (dopamine B-hydroxylase in vesicle)

Question 2

Describe how is noradrenaline broken down after release

Answer 2

Neuronal breakdown: MAO-A (monoamine oxidase A)

Peripheral breakdown: COMT (catechol-O methyltransferase)

Question 3

What are the subdivision of adrenoreceptors

Answer 3

a1: located on the post-synaptic neurone and elicit vasoconstriction
a2: located on pre-synaptic neurone and inhibit effect
B1: stimulatory to the heart and inhibitory to GIT and kidneys
B2: on bronchial, uterine
*a1 uses Gq, a2 uses Gi, beta uses Gs

Question 4

List both natural and synthetic adrenoceptor agonists and their target receptors. Describe their effects

Answer 4

Noradrenaline (a1, a2, B1): potent vasoconstrictor and increase BP, but reduce HR
Adrenaline (a1, a2, B1, B2): increase HR and decrease DBP
Dopamine (weak on a1 and B1)
Isoprenaline (B1 and B2): increase HR significantly and no effect on MBP
Phenyleprhine (a1)

Question 5

Describe the effect of binding to adrenoceptors on some vascular beds

Answer 5

Skin: a receptors - NA, AD cause vasoconstriction
Visceral: a receptors - same as skin
Renal: a receptor and B1 - same as skin
Coronary: a and B1 - NA, AD and isoprenaline cause vasodilation
Skeletal muscle: a and B2: NA causes vasoconstriction and AD and isoprenaline cause vasodilation

Question 6

Name the drug that inhibit ACE and Ang II Type 1 receptor

Answer 6

Captopril

Losartan

Question 7

List the stimuli that cause the release of renin

Answer 7

B1 receptor activation on juxtaglomerular cells
Reduced renal prefusion
Low NaCl sensed by macula densa

Question 8

List potential pharmacological targets to manipulate renin release

Answer 8

ACE inhibitor (Captopril)
Angiotensin Type 1 receptor inhibitor (Losartan)
Renin receptor blockers
Beta blocker
Loop diuretics
NSAID

Question 9

Describe the effects of angiotensin in terms of peripheral resistance, renal function and cardiovascular structure

Answer 9

TPR:
1) direct vasoconstriction
2) increase release and reduce reuptake of NA
3) increase sympathetic activity
4) release catecholamine from adrenal gland
Renal function:
1) increase NaCl reabsorption
2) altered renal haemodynamics: renal artery vasoconstriction and enhanced effect of NA on kidneys
3) aldosterone release
CV structure
1) increase wall stress and increase preload and afterload
2) increase expressions of proto-oncogenes, growth factors and increase ECM proteins

Question 10

What are the stimuli for the release of aldosterone

Answer 10

Angiotensin II
ACTH
Increase in K+ concentration - most important trigger

Question 11

How do you distinguish between primary and secondary hyperaldosteronism

Answer 11

Primary: high BP and no oedema
Secondary: low/normal BP and high oedema

Question 12

What is the body’s reflex to stress such as fluid loss

Answer 12

Activation of both sympathetic nervous system and renin-angiotensin system

1) increase CO and stroke volume
2) increase BP
3) increase salt and water retention
4) coagulation (with decreased fibrinolysis)
5) Platelet activation