Vascular smooth muscle

Question 1

sympathetic vasoconstrictor fibre

what does it release and where does it act on?

Answer 1

will release noradrenaline which act on vascular smooth muscle cells

Question 2

collagenous connective tissue - function

Answer 2

connective tissue to give it structure

Question 3

vasa vasorum

fucntion?

Answer 3

small blood vessels to supply o2 + nutrients to blood vessels itself

Question 4

intima

what is it?

Answer 4

epethelial layer

Question 5

media layer

what is it?

Answer 5

vascular smooth muscle cells (contraction/relaxation will change size of lumen)

Question 6

Adventitia

what two things are here?

Answer 6

mechanical structural area of the blood vessel

nerves innervate the blood vessel

Question 7

what is vascular tone?

what controls vascular tone?

Answer 7

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)

Question 8

What vessels is vascular tone present in?

what doesn’t have vascular tone?

Answer 8

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

Question 9

What is vascular tone normally like?

importance of this?

Answer 9

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

Question 10

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

Answer 10

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

Question 11

general fetaures of regulation of vascular tone

where does the constrictor response act?
dilator response?

Answer 11

Constrictor responses: act directly at VSMCs

Dilator responses: indirectly via endothelium

Question 12

why have intrinsic/local controls?

name some examples of instrinsic controls
why?
importance of this?

Answer 12

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

Question 13

why have extrinsic controls?

what do they regulate? and what does that regulate?

what does the brain do during exercise?

Answer 13

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

Question 14

what are external or extrinsic controls?

name the vasoconstrictor/dilator hormones and neurotransmitters

Answer 14

Vasoconstrictors - noradrenaline
Vasodilators - Ach, nitric oxide (Endothelium lecture)

Hormones
Vasoconstrictor - adrenaline, angiotensin II, vasopressin
Vasodilators - ANP

Question 15

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

Answer 15

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

Question 16

where do the sympathetic postganglionic fibres synapse at the blood vessel?

layer? and where?

Answer 16

at the adventita layer

synapse at bead like structures called varicoses + release NA

Question 17

Neurotransmission of sympathetic vasoconstrictor

what is stimulated? effect? what is released? where do these act on? (receptor)

Answer 17

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)

Question 18

Feeback/end of the neurotransmission

what is the negative feedback loop?
what happens to NA?

Answer 18

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

Question 19

Neuromodulation of the sympathetic vasoconstrictor nerve

what will have a positive effect?
what molecules have a negative effect?

Answer 19

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

Question 20

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)

Answer 20

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

Question 21

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?

Answer 21

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

Question 22

sympathetic vasoconstrictor - arterioles

what do they produce and effect of this?

Answer 22

Contract resistance arterioles -> Produces vascular tone

This allows vasodilatation/increased blood flow to occur

Question 23

Distinct RVLM neurones-sympathetic pathways innervate different tissues

what does this mean?
name an example of this taking place

Answer 23

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)

Question 24

Pre-capillary vasoconstriction

what will this do to the capillary?
effect of this?
importance of this?

Answer 24

Decreased capillary pressure due to pressure drop

Increased absorption of interstitial fluid into blood plasma to maintain blood volume (important in hypovolemia)

Question 25

Control TPR name the two equations what does control of this maintain?

Answer 25

maintains arterial blood pressure and blood flow to brain/myocardium since Pa = CO x TPR and BF = Pa / TPR

Question 26

sympathetic vasoconstrictor controls venous blood volume where is most blood at rest? what will constriction do?

Answer 26

(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

Question 27

hormones affecting vsmcs name vasoconstrictor hormones (3) name vasodilator hormones (1) name other hormones

Answer 27

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

Question 28

role of hormonal control of vsmcs physiology - what does it control and what does it maintain? pathology - what can go wromg? name 2 conditions

Answer 28

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

Question 29

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?

Answer 29

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

Question 30

renin to angiotensin II describe the sequence - what does renin do and where does this molecule go?

Answer 30

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

Question 31

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)

Answer 31

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

Question 32

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?

Answer 32

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

Question 33

how do left arterial receptors and arterial baroreceptors respond to large decrease in blood volume? name the pathways and what is released?

Answer 33

``` Drop in blood volume, e.g. haemorrrhage Switches off NTS-CVLM inhibitory pathway Switching on CVLM-SON/PVN excitatory pathway –  ADH release ```

Question 34

effects of ADH effect at high conc? what does it act on? normal role? where? what does it act on?

Answer 34

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

Question 35

receptors for vasoconstrictors ``` receptors for na/ ad ang II adh et-1 txa2 ```

Answer 35

``` Receptors NA / Ad : α1 Ang II : AT1 Vasopressin : V1 ET-1 : ETA TXA2 : TP ```

Question 36

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)

Answer 36

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

Question 37

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?

Answer 37

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

Question 38

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?

Answer 38

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