Neural regulation of blood vessels Lecture 9 Flashcards
What nerves supply blood vessels?
Most vessels have only sympathetic innervation
Perivascular verve fibres in the adventia-media border and do not penetrate into the vascular smooth muscle within the blood vessel
Vasoconstrictor- NA, ATP, NPY
Dilator- ACh, VIP and NO
Except from the cerebrum, heart, and reproductive tissue which also have parasympathetic ACh, VIP NO
Describe varicosities
Granular vesicles contain NA ATP
Large opaque vesicles contain NPY
Vesicles are sites of release of neurotransmitter - action potential passing through varicosity open Ca2+ channels cuasing vesicle to fuse with membrane and discharge NA and ATP.
Release is as the action potential passes (en passant)
NA production is matched to nerve activity
Increase nerve activity leads to increased enzymatic activity in the conversion of tyrosine to DOPA to dopamine to NA within cytoplasm where NA is taken up into a vesicle.
There is also re-uptake via a NA transporter
After release they act on alpha1 and alpha2 receptors on the vessel and diffuse into the blood stream or broken down by COMT, act on pre-synaptic alpha2 inhibition receptors, re-uptake, break down by MAO. NA can also act on a2 receptors presynaptically by inhibiting itself.
Describe the differential distribution of adrenoceptors
In many tissues, nerve released NA stimulates alpha 1 and 2 recptors on proximal arterioles.
There are fewer alpha1 receptor and lots of alpha 2 in vessels as you approach the distal arterioles
Their constrictor influence is more easily blunted by local dilator influences
List some agonist as and antagonist to alpha receptors
A1 agonist- phenylephrine
A1 Antagonist- prazosin
A2 agonist- clonidine
A2 Antagonist- yohimbine
Non selective agonist- phenylephrine
Describe the effects of NA on VSM via A1 and A2 receptors
When NA binds to A1- stimulates PLC to convert PI to InsP3 which acts triggers the release of more intraceullar Ca2+ from the sarcoplasmic reticulum. Can also Stimulates voltage gated Ca channels leads to influx of Ca
When NA binds to A2- activation leads to the inhibition of K channels leading to depolarisation and activation of voltage gated Ca channels leading to an influx of calcium Increased intracellular calcium leads to contraction
Describe the release and action of co-transmitter ATP and NA
Purinergic receptors- P1 binds adenosine
P2 binds ATP ADP AMP (P2X-1 on VSM and P2Y I. The endothelium)
ATP is metabolised by ecto-nucleotidases to AMP and then to adenosine by 5’ nucleotidases
Adenosine acts on pre-synaptic P1 receptors inhibiting ATP release ATP primes the VSM for the action of NA
Effects of ATP And NA: ATP binds to P2XI receptor which when stimulated allows small charged ions through (Ca, Na) hepling to depolarise the membrane and open up the Ca channels. ATP is quiker than NA so this process is done first which depolarises the VSM membrane causing NA to come and act on alpha 1/2 recptors
Describe neuropeptide Y (NPY)
Discharged with long periods of high frequency activity
Produces slow and long-lasting constriction, particularly in the presence of NA
Y1 main receptor in VSM
Y2 pre-junctional, modulates NPY/ATP/NA release
Terminated by peptidases
Facilitated vasoconstriction evoked by ATP and NA
Released in order to prevent a catastrophic fall in ABP in the case of haemorrhage, dehydration, shock and heart failure
Describe the synthesis and release of ACh VIP and NO
Ach is made from acetyl COA and choline by Choline Acetyltransferase. VIP is also made in varcosities and taken into vesicles. Ach diffuses through VSM onto muscarine recpeotrs of endothelial cells. This triggers the NO pathway to make NO which causes vasodilation. Ach is broken down by AchE and taken back as choline bt a choline carrier where it can be made back into Ach. Acetate diffuses away from blood stream.
VIP acts on VIP receptors on VSM which prodcues vasodilation. VIP is broken down bt peptidases found in intersitial fluid. An action potential activates all these processes (VIP,Ach) passing through. An increase in Ca levels in cytoplasm stimulates nNOS to release NO.
Describe the mechanisms of action of nerve released ACh VIP and NO on VSM
Mechanisms of action of Ach,VIP and NO:
Ach diffuses through VSM to act on endothelial cells by triggereing eNOS to make NO. NO binds to guanylate cyclase to form cGMP which causes vasodilation.
VIP open K+ channels causing hyperpolarisation which helps close Ca chanels.
nNOS diffuses into VSM as NO and binds to guanylate cyclae which generates cGMP which causes dilation
A decrease in calcium levels cause VASODILATION
Describe cholinergic active dilator fibres
In skin = allow greater vasodilation in response to heat
In penis - allows erection
