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L9 Neural Regulation of Blood Vessels
All blood vessels have symp  constriction
Descending symp nerves have tonic excitatory activity = blood vessels are always slightly constricted (decreased
activity  dilation)
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Autonomic nerves use co-transmitters
Sympathetic vasoconstrictor: NAd, ATP + NPY (neuro peptide Y)
Sympathetic dilator:
o ACh, + vasoactive intestinal peptide (VIP) + NO
 Skin in some regions
Parasympathetic cholinergic: ACh + VIP + NO
o Cerebral, coronary, reproductive tissue

Arrangement of sympathetic nerve fibres
 Paravascular nerve bundles send out branches to form perivascular network with varicosities
 Perivascular nerve fibres are in adventitial-media border; don’t enter the VSM
 Effect of nerve activity on VSM must be conducted from cell to cell
Varicosity
 Granular vesicles contain NA, ATP
 Large opaque vesicle contain NPY
 Sites of release of transmitters
 Release is “en passant”
o When action potential passes through varicosity as it travels through along nerve fibres
o Increased Ca2+ leads to release a bit of NAd
Biosynthesis of NAd
 Mainly made in varicosity
 Tryrosine from the blood stream
 Usually re-uptake to stop its effect
Release of NAd + termination of action of NAd
 Act mostly on α1 receptors (sometimes on
α2)
 Have pre-synaptic α2 receptors – helps
control the release of NAd
 NAd can:
o Diffuse in to blood stream
o RE-UPTAKE
α1 receptors all along proximal arterioles (the
bigger ones)
α2 receptors on distal arterioles – their constrictor influence is more easily blunted by local dilator influences
(metabolites)
NAd binds to α1:
1
...
Open voltage gated channels on VSM  depolarisation  sarcoplasmic reticulum release Ca2+
NAd binds to α2:
1
...

 P2 receptors – ATP, ADP, AMP – P2X acts on VSM
 P2X receptors are channels – open when ATP binds – allow +ve ions into the cell  further depolarisation (help
to open voltage gated Ca2+ channels)
 ATP initiates the response then NAd causes the biggest part of the response
 ATP ‘primes’ the VSM for the action of NAd
 ATP and NAd facilitate each other’s effects
NPY
 In large opaque vesicles
 When there is high frequency of nerve action potential (high symp nerve activity)
 Produces slow and long-lasting constriction
o Particularly in presence of NAd
 Y1 receptors on VSM
 Y2 – pre-junctional – modulates NPY/ATP/NAd release
 Termination of action – peptidases
 NPY facilitates vasoconstriction evoked by ATP and NAd
 NPY released when symp activity is very high
o Haemorrhage, dehydration, shock, heart failure etc
o May prevent catastrophic fall in ABP
Range of response to change in nerve activity
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Max stimulation of symp NAd nerves  large
decrease in blood flow
If you block the symp NAd nerves  increase in
blood flow (not to max - max dialtion achieved
by metabolic activity)
Some vessels have active dilator fibres that
allow them to get closer the the maximal
dialtion
o Cutaneous circulation of arm, legs,
torse
o Penis, uterus, vagina
o Ceregral circulation
o Coronary circulation
Co-transmission of ACh, VIP and NO

Synthesis and release of ACh, VIP and NO
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In varicosity that contain vesicles (hold the ACh and VIP) in the cytoplasm there is nNOS
Acetyl CoA + Choline  CoA + ACh (catalysed by Choline acetyl transferase)
If ACh is released:
o Defuses through VSM to muscarinic receptors on vascular endothelium
o Stimulates NOS  NOS released  VSM  stimulates guanalate cylase  cGMP  relaxation of VSM
o Acetylcholine esterase breaks it down
...
Acetate into the blood stream
VIP into receptor which is coupled +vely to K+ channel  efflux  hyperpolarisation  closes voltage gated
channels  decreased [Ca2+]  relaxation

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o Broken down by pepitases that are stuck to the VSM membrane
Increase in Ca2+ from the AP through the varicosity stimulates nNOS  NO  GC  cGMP  relaxation
cGMP reduces sensitivity of myosin cross linking to Ca2+  relaxation

Cholinergic Active dilator fibres
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In skin (symp) – allows great vasodilation in response to heat
In penis (parasymp) – allows erection
o NB silendifil (PDE inhibitor) inhibits cGMP breakdown of VSM
o Helps treat impotence
In cerebral circulation (parasymp) – involved in pressure autoregulation ??
In coronary circulation (parasymp) - ??
In skeletal muscle of cats and dogs (symp)



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