L15 Vascular function 2

Question 1

Describe the steps in neurotransmission from sympathetic pre-synaptic nerve - including neurotransmitter, receptor

Answer 1

1. Increased depolarisation = increased activity
2. Increased chance of releasing vesicles of neurotransmitter
   = NA or A + others depending on which organ
3. Vesicles fuse with cell membrane releasing neurotransmitter into synaptic cleft.
4. a) NA bind to post synaptic receptor : a1&raquo_space;a2
   b) binds to presynaptic receptor as a - feedback signal: reduce depolarisation and vesicle release
   c) diffuse into blood supply and get metabolised

Question 2

How does inhibitory vs excitatory modulation of adrenergic neurotransmission work (3)

Answer 2

Inhibitory: eg. adenosine (muscle metab), histamine, aCh

1. Bind presynaptic/post synaptic receptors so
   - Same amount of NA has less effect
   - ->less vasoconstriction

Excitatory: eg. ang 2, adrenaline

1. If circulating:
   For a given level of depolarisation in these cells,
   -more NA release
2. If increased AT1 receptor activation on post synaptic neuron
   - for given NA, intracellular mechanisms are amplified
3. For muscle circulating adrenaline acts on precapillary B2 receptors for vasodilation

Question 3

What are the 2 endogenous symp neurotransmitters and what receptors do they act on in the blood vessels - how many, causing what effects?

Answer 3

Noradrenaline, Adrenaline.

Are able to act on all 3 receptors, but have different affinities.

a1: active vasoconstriction (Ca2+ increase)
a2: inhibit vasodilation
b2: active vasodilation

Variation in amount of post synaptic a2 vs B2 receptors lead to different overall vasoconstriction & vasodilation bc same substrate does both

Question 4

Compare  Adrenaline (A) vs Noradrenaline (NA)
->receptor affinity, effect on organ blood flow- blood vessels

Answer 4

Adrenaline has greater/same affinity as NA for alpha receptors (constriction)

But Adrenaline has much greater affinity for Beta receptors (dilation) than NA

1. Adrenaline
   Causes vasodilation in
   - skeletal muscle
   - splanchnic

Causes vasoconstriction

• skin
• kidney

2.Noradrenaline
Causes vasoconstriction in all (sans coronary/cerebral)

• Skeletal muscle
• skin,
• kidney,
• splanchnic

Question 5

What’s the parasympathetic neurotransmitter, receptor, site, effect - effect in pathology

Answer 5

1. Parasympathetic innervation -> release of ACh -acetylcholine
2. Circulating ACh binds to M3 muscarinic receptors in Endothelium of bv
3. Stimulates release of NO–>vasodilation
4. Pathology: if endothelium absent, ACh can act directly on muscarinic receptors on VSM to cause Vasoconstriction

Question 6

How is blood flow to skeletal muscle increased during exercise and how does exercise intolerance come about

Answer 6

• There is increased symp and autoregulation to cause vasoconstriction
• This is overcome by the large amount of metabolic products which cause vasodilation

–>damage to endothelial NO release can lead to less vasodilation to overcome symp/auto vasoconstriction than normal = exercise intolerance

Question 7

How does sympathetic activation in skin and sweat glands promote thermoregulation

Answer 7

With skin the affinity of alpha receptors for NA decreases with increasing temperature

–>more vasodilation when hot.

Sympathetic cholinergic activation of sweat glands activates kinin cascade

• dilation of precapillary vessels
• constriction of post capillary
• increase capillary permeability

Question 8

What factors affect the autoregulation of cerebral blood flow: dogma vs reality

Answer 8

• Small changes in PaCO2 –>increase flow
• Big changes in PaO2–> increase flow

Reality : There is proportional relationship between cerebral blood flow and perfusion pressure (MAP) within one subject.

Dogma: Among groups of subjects with different MAP, the cerebral blood flow is same if their perfusion pressure is in range of 60-180 Hg. (autoregulation can protect against drops in MAP)- not true