Vascular smooth muscle Flashcards
sympathetic vasoconstrictor fibre
what does it release and where does it act on?
will release noradrenaline which act on vascular smooth muscle cells
collagenous connective tissue - function
connective tissue to give it structure
vasa vasorum
fucntion?
small blood vessels to supply o2 + nutrients to blood vessels itself
intima
what is it?
epethelial layer
media layer
what is it?
vascular smooth muscle cells (contraction/relaxation will change size of lumen)
Adventitia
what two things are here?
mechanical structural area of the blood vessel
nerves innervate the blood vessel
what is vascular tone?
what controls vascular tone?
describes the degree of constriction of a blood vessel relative to maximum dilation
Vascular tone controlled by contractile state
of vascular smooth muscle cells (VSMCs)
What vessels is vascular tone present in?
what doesn’t have vascular tone?
Vascular tone present in all vessels containing VSMCs
– arteries, arterioles, veins (r4 controls resistance to circulation therefore controls vascular tone)
Capillaries do not contain VSMCs so do not have vascular tone
What is vascular tone normally like?
importance of this?
normally blood vessel will look like middle blood vessel hence not dilated max or constricted max therefore in the middle
This is important because it will have some contractile properties already contracting hence can open up or constrict further according to the situation
what regulates vascular tone?
4 main groups?
how does each group regulate vascular tone?
what are the different nerves and what do they release?
name some of the other key molecules
metabolic factors - adenosine, k+, h+ -> if we do more work, we produce more metabolic factors from cells in end organs + tissues which feedback for dilation to increase bloodflow for o2 + nutrients
adventitia nerves sympathetic vasoconstrictor nerves - NA sympathetic vasodilatornerves - ach parasympathetic vasodilator nerves - NO perivascular sensory nerves - sub P
endothelila lining
constrictors ET-1
dilators - NO, K+, PGI2
blood itself Hormones - Adr, Ang II, ADH, ANP Platelets –TXA2 Immune cells - Histamine Stretch
general fetaures of regulation of vascular tone
where does the constrictor response act?
dilator response?
Constrictor responses: act directly at VSMCs
Dilator responses: indirectly via endothelium
why have intrinsic/local controls?
name some examples of instrinsic controls
why?
importance of this?
e.g. Role of endothelium, immune cells, platelets (for injury), stretch
Regulate local blood flow to organs/tissues
Important – regional hyperaemia -> if muscle needs more o2/glucose, more blood flow regionally
why have extrinsic controls?
what do they regulate? and what does that regulate?
what does the brain do during exercise?
Regulate TPR to control blood pressure
Blood pressure is the drive for blood flow
Brain function selectivity alters blood flow to organs according to need
e.g. During exercise, thermoregulation etc.
The brain is linked to various nerves that control blood vessels
what are external or extrinsic controls?
name the vasoconstrictor/dilator hormones and neurotransmitters
Vasoconstrictors - noradrenaline
Vasodilators - Ach, nitric oxide (Endothelium lecture)
Hormones
Vasoconstrictor - adrenaline, angiotensin II, vasopressin
Vasodilators - ANP
general outline of the sympathetic vasoconstrictor system
what recieves info and from where?
where does this send info to?
name 2 locations and via what fibres the info can go to from here
Most widespread and important extrinsic control of circulation
Rostral ventral lateral medulla (RVLM) receives info from CVLM, hypothalamus and sends down info in an excitatory drive to the thoraric spinal cord intermediolateral (IML) where sympathetic pregaglionic branch out to sympathetic ganglia.
sympathetic postganglionic fibre sends info to the heart (b1), releases noradrenaline to a1,b2 receptors at blood vessels
sympathic preganglionic fibre can also go to adrenal medulla which release adrenaline and affect a1,b2 receptors at blood vessels
where do the sympathetic postganglionic fibres synapse at the blood vessel?
layer? and where?
at the adventita layer
synapse at bead like structures called varicoses + release NA
Neurotransmission of sympathetic vasoconstrictor
what is stimulated? effect? what is released? where do these act on? (receptor)
stimulation of postganglionic fibres Ap travelling along fibres reach variscosity where ca2+ influx Ca dependent vesicle release of NA NA released will act on A1 receptors on smooth muscle cell on medial layer therefore produce constriction (can act on A2 receptors to cause constriction too)
Feeback/end of the neurotransmission
what is the negative feedback loop?
what happens to NA?
large amount of NA can feedback to A2 which will switch off the process therefore less NA released
NA will be re-uptaken back into varicosity therefore recycled
Neuromodulation of the sympathetic vasoconstrictor nerve
what will have a positive effect?
what molecules have a negative effect?
angiotensin II has +ve effect on the variscosity therefore stimulate the release of more NA
K+, adenosine, PGE1, histamine, serotonin and ACh can switch off the sympathetic system hence less vasoconstriction and will open up vessels
stimulation at the pre and post synaptic membrane of the sympathetic vasoconstrictor
name the receptors of the post synaptic membrane and the effect stimulation will have
name the receptors of the pre synaptic membrane and the effect stimulation will have (and the negative feedback loop)
Post-synaptic membrane
α1 – contraction, α2 – contraction, β2 - relaxation (adrenaline acts on B2 receptors)
Pre-synaptic membrane
AT1 – increase release of NA (RAAS increase sym activity) via angiotensin II
α2 – reduce release of NA via negative feedback
K+, adenosine etc. – reduce release of NA – important vasodilatation pathway
summary of sympathetic vasoconstrictor
what is this controlled by? main centre? controlled by? what does it provide control of?
what does it innervate? what is released and where does this act + effect of this?
what kind of activity is sympathetic activity? what does this mean and what will a fall in this activity do?
clinical importance of this?
Controlled by brainstem
RVLM (vasomotor centre) – controlled by other areas, CVLM, hypothalamus
Provides central control of blood flow and blood pressure
Innervate most arterioles & veins of the body
NA activates a1-adrenoceptors on vascular smooth muscle cells
a1-adrenoceptors cause vasoconstriction
Sympathetic nerve activity is TONIC (they fire about 1 action potential / s)
Tonic sympathetic activity sets vascular tone
This means that a FALL in ongoing sympathetic activity produces vasodilatation
Decrease in mechanisms coupling sympathetic activity to vascular tone is an important principle in pharmacological treatment of cardiovascular disease
e.g. hypertension
sympathetic vasoconstrictor - arterioles
what do they produce and effect of this?
Contract resistance arterioles -> Produces vascular tone
This allows vasodilatation/increased blood flow to occur
Distinct RVLM neurones-sympathetic pathways innervate different tissues
what does this mean?
name an example of this taking place
Switching on vasoconstriction in some vessels
whilst switching off – producing vasodilation - in other vessels
e.g. During exercise, Increased sym nerve stimulation to GI (less blood flow), Reduce sym nerve stimulation to skin (more blood flow, cool down)
Pre-capillary vasoconstriction
what will this do to the capillary?
effect of this?
importance of this?
Decreased capillary pressure due to pressure drop
Increased absorption of interstitial fluid into blood plasma to maintain blood volume (important in hypovolemia)
Control TPR
name the two equations
what does control of this maintain?
maintains arterial blood pressure and blood flow to brain/myocardium since Pa = CO x TPR and BF = Pa / TPR
sympathetic vasoconstrictor controls venous blood volume
where is most blood at rest?
what will constriction do?
(at rest 2/3rd blood in veins)
Venoconstriction so decrease venous blood volume and increase Venous return and increase stroke volume via Starling’s law
hormones affecting vsmcs
name vasoconstrictor hormones (3)
name vasodilator hormones (1)
name other hormones
Vasoconstrictors
Adrenaline, Angiotensin II (Ang II), Anti-Diuretic Hormone (ADH)
Vasodilators
Atrial natriuretic peptide (ANP)
Others, e.g. Insulin, Oestrogen, Relaxin
Also effects on vasculature
role of hormonal control of vsmcs
physiology - what does it control and what does it maintain?
pathology - what can go wromg? name 2 conditions
Physiology
Control appropriate blood flow/blood pressure during activity (exercise, standing) + maintain blood flow/blood pressure to essential organs (brain, heart) during haemodynamic crisis (haemorrhage, dehydration)
Pathology
Excess production of these agents often associated with excess vasoconstriction and vascular disease – hypertension, heart failure
vasoconstrictor hormones
where is adrenaline released from? due to? how does it act differently at high conc?
how is angiotensin II formed? where does it act on?
where is ADH released from? where does it act on at high conc?
where is endothelin-1 (ET1) released from? where does it act on?
where is thromboxane released from? where does it act on? other role?
Adrenaline (Adr):
Released due to sympathetic nerve stimulation
Mainly from adrenal glands
At high concentrations acts on a1-adenoceptors on VSMCs (instead of B2 at high conc)
Angiotensin II (Ang II): Formed from RAAS Very potent vasoconstrictor Acts on AT1 receptors on VSMCs
ADH (Vasopressin): Released from posterior pituitary
High concentrations acts on V1-receptors on VSMCs
Other important vasoconstrictors
Endothelin-1 (ET1): Released from endothelium
Acts on ETA receptors on VSMCs
Thromboxane (TXA2): Released from aggregating platelets
Acts on TP receptors on VSMCs
Important vasoconstriction alongside clotting process
renin to angiotensin II
describe the sequence - what does renin do and where does this molecule go?
RAAS system begins with the release of renin
angiotensin 1 goes through circulation + goes into the lungs where we find ACE (found in the lungs as it recieves all the CO therefore all that comes out of rhs of heart goes into lungs)
therefore large proportion of angiotensin 1 will be converted into angiotensin 2
effects of angiotensin II
3 effects
where central effect?
effect on adrenal gland? what is released and effect of this?
how can it act on vessels? (2)
It can have central effects on the brain hence increase the sympathetic drive
It can cause the adrenal gland to release aldosterone which acts on the kidney to release NaCl + H2O for more water retention hence increase blood volume and therefore pressure
It can act on the AT1 receptors on vessels to cause vasoconstriction and it can stimulate sympathetic nerves in vessels to release NA therefore increase constriction and increase TPR
how do left arterial receptors and arterial baroreceptors respond to increase in blood volume?
what do they respond to? where are signals sent and effect of this?
what is the last pathways and effect of this?
They respond to stretch hence an increase in blood volume/pressure will stimulate them causing them to send signals to the NTS, switching it on, hence sending an inhibitory pathway to the CVLM
This will mean there is no excitatory pathway to the hypothalamus hence doesn’t cause pathway to release ADH therefore there will be a drop in BP/volume
how do left arterial receptors and arterial baroreceptors respond to large decrease in blood volume?
name the pathways and what is released?
Drop in blood volume, e.g. haemorrrhage Switches off NTS-CVLM inhibitory pathway Switching on CVLM-SON/PVN excitatory pathway – ADH release
effects of ADH
effect at high conc? what does it act on?
normal role? where? what does it act on?
VSMCs
(Only at high concentrations)
Vasoconstriction - V1 receptors - During hypovolemia
Kidney
(normal role)
V2 receptors -Insertion of aquaporin channels in collecting duct leading to H2O reabsorption and increased Blood volume
receptors for vasoconstrictors
receptors for na/ ad ang II adh et-1 txa2
Receptors NA / Ad : α1 Ang II : AT1 Vasopressin : V1 ET-1 : ETA TXA2 : TP
Vasoconstrictors increase vascular tone by activating
same G-protein-coupled pathway in VSMCs
what pathway is this? hence what molecules are made?
effect of this and what 2 ways lead to Ca2+ influx?
essential points? (2)
Gq pathway hence PIP2 to DAG and IP3 via PLC
DAG increase membrane excitability leading to depolarisation leads to activation of voltage-gated
Ca2+ channels (VGCCs) which induces Ca2+ influx
IP3 acts on IP3 receptors on the SR to release ca2+ too which leads to contraction
Essential points:
(1) Requires depolarisation –
activation of VGCCs – Ca2+ entry
(2) Requires Ca2+ release
Vasodilator hormone - Atrial Natriuretic Peptide (ANP)
what releases this?
what causes the release of this?
where do they act on?
what pathway do they increase?
how can this be a biomarker for poor heart function?
Released by specialised atria myocytes
Secreted by increasing filling pressures which stimulate stretch receptors
Act at NP receptors on VSMCs - increase cGMP pathway
(like nitric oxide, see Endothelium lecture)
Biomarker for poor heart function/congested circulation – e.g. heart failure as congested heart means more blood in atriatherefore will stretch receptors and release ANP
How does ANP reduce blood pressure?
what does it oppose the action of?
what does it increase the dilation of? effect of this?
what 3 molecules does it decrease the release and action of?
Reduces blood pressure by:
Systemic vasodilatation – opposes action of NA, Adr, Ang II, ADH, ET-1, TXA2
Dilation of renal afferent arteriole - Increase Glomerular filtration rate
Increase Na+ and H2O excretion by the kidney - decrease Blood volume
decrease release and actions - aldosterone, renin, ADH
