7) Nervous & hormonal control of vascular tone Flashcards
1
Q
What is a paracrine signal?
A
- When a cell produces a signal that affects another cell nearby or next to it. (A cell that produces a hormone may affect a cell next to it or a few cells away)
2
Q
What is an autocrine signal?
A
- When a cell produces a signal that affects itself
3
Q
What are the local and extrinsic factors that control blood flow?
A
- Local: Myogenic (muscular) response, paracrine and autocrine signalling, physical factors (e.g. temp or stress)
- Extrinsic: Parasympathetic, sympathetic and sensory vasodilator nerves, Sensory vasoconstrictor nerves and hormones such as adrenaline, vasopressin, etc.
4
Q
What part of the brain controls blood flow?
A
- The medulla oblangata
5
Q
Describe the route of a sympathetic vasoconstrictor system.
A
- A main excitatory drive is sent from the medulla oblongata down the spinal chord.
- It emerges as preganglionic neurones between T1-L2 and enter sympathetic ganglia
- From here it travels down final sympathetic post-ganglionic fibres which innervate all vessels, adrenal glands and the heart
- Noradrenaline is mainly released at the site of the heart and vessels.
- Noradrenaline causes constriction of vessels (in alpha-1 adrenoreceptors) and causes heart rate and stroke volume to increase in the heart (beta-1 adrenoreceptors) as the heart beats harder and faster
- There is some parasympathetic innervation to the adrenal medulla which causes adrenaline to be released.
- Adrenaline interacts with beta-2 adrenoreceptors causing relaxation in vessels
6
Q
Explain how an action potential causes contraction/ relaxation in smooth muscles.
A
- An action potential moves down the axon and arrives at varicosities (beads on a string) found in the adventitia layer.
- This causes depolarisation of the varicosities which activate voltage gated Ca2+ channels leading to an ingress of calcium ions.
- This ingress makes the cells release neurotransmitters (mainly noradrenaline)
- Noradrenaline diffuses into the smooth muscles where it binds mainly to a1 adrenoreceptors (causing contraction), a2 adrenoreceptors (causing some contraction) and b2 adrenoreceptors (causing relaxation)
- The noradrenaline can then be taken up again and recycled or broken down
7
Q
How are responses of contraction and relaxation modulated in the smooth muscles?
A
- Depending on what receptors are present
8
Q
What can increase the release of noradrenaline?
A
- Angiotensin II acts on AT1 receptors increasing noradrenaline release
9
Q
What can inhibit noradrenaline release?
A
- Metabolites can prevent vasoconstriction to maintain blood flow through feedback and inhibiting noradrenaline release
- Noradrenaline can also negatively feedback itself through a2 adrenoreceptors to limit noradrenaline release
10
Q
Why does the required vasodilation and vasoconstriction take place?
A
- Lots of modulation occurs at varicosities
11
Q
What part of the medulla oblongata controls sympathetic vasoconstrictor nerves?
A
- The Rostral Ventrolateral Medulla (RVLM) provides central control of blood flow and blood pressure
- It is controlled by the Caudal Ventrolateral Medulla (CVLM) and the hypothalamus
12
Q
What sets vascular tone?
A
- The tonic sympathetic activity.
- Sympathetic activity is tonic which means there is an action potential fired every second
13
Q
What are the main roles of sympathetic vasoconstrictor nerves?
A
- Different sympathetic pathways that innervate different tissues allow us to vasoconstrict some vessels and vasodilate others
- Precapillary vasoconstriction which causes pressure drop in capillary leading to increased absorption of interstitial fluid into the blood plasma to maintain blood volume
- Control resistance arterioles which allows increased blood flow to occur (to the brain, heart and kidneys)
- Controls venous blood volume. Venoconstriction leads to decreased venous blood volume. This increases venous return which increases stroke volume through Starling’s law
14
Q
How does vasodilation occur?
A
- Turning off vasoconstriction
- Through vasodilator nerves
15
Q
What are vasodilator nerves?
A
- Parasympathetic nerves that control a vascular bed rather than global functions.
- These nerves release acetylcholine which binds to muscarinic receptors on smooth muscles.
- On binding to M3 receptors, on vascular endothelium, they cause vasodilation through the formation of nitric oxide (NO)
- On binding to M2 and M3 receptors, in smooth muscles, they cause contraction
16
Q
Where is adrenaline released from?
A
- Adrenaline is released from the adrenals within the medulla oblongata through the action of acetylcholine on nicotinic receptors.
- Adrenaline is made during exercise, a Fight-or-Fight situation, hypotension and hypoglycaemia
17
Q
What effect does adrenaline have on the body?
A
- Increases glucose mobilisation
- Increases heart rate and stroke volume during exercise
- Causes vasodilation of coronary and skeletal muscle arteries
18
Q
Describe the action of adrenaline/noradrenaline on a1 adrenoreceptors.
A
- The neurotransmitter binds to a1-adrenoreceptor which activates phospholipase C
- Active phospholipase C metabolises PIP2 to IP3 and DAG which causes the release of Ca2+
- Ca2+ leads to smooth muscle contraction
19
Q
Describe the action of adrenaline/noradrenaline on a2 adrenoreceptors
A
- The neurotransmitter binds to the receptor causing the inhibition of adenylate cyclase.
- This means ATP is unable to be processed into cAMP and smooth muscles do not contract (causing muscle relaxation)
- Furthermore it inhibits Ca2+ in a negative feedback system preventing the release of transmitters
20
Q
Describe the action of adrenaline/noradrenaline on B1 and B2 receptors.
A
- The neurotransmitter binds to the receptor causing the activation of adenylate cyclase.
- This leads to the conversion of ATP to cAMP.
- In B1 this leads to heart contraction
- In B2 this leads to vasodilation
21
Q
Which receptor is the main cause of vasoconstriction?
A
- A1 adrenoreceptors
22
Q
Describe the distribution of the two adrenoreceptors in skeletal muscles and coronary arteries
A
-Skeletal muscles contain more B2 than A1 adrenoreceptors
23
Q
Which receptor has a higher affinity for adrenaline?
A
- Beta adrenoreceptors
- They mainly bind to B2-adrenoreceptors to dilate vessels
24
Q
Which receptor has a higher affinity for noradrenaline?
A
- Alpha adrenoreceptors
- They mainly act at A1-adrenoreceptors to constrict vessels
25
What are the effects of adrenaline on different tissues?
- In most tissues (e.g. GI tract) we experience vasoconstriction through the activation of a1 adrenoreceptors
- In skeletal muscles and coronary circulation we experience vasodilation through the activation of B2 adrenoreceptors.
26
What are the effects of noradrenaline on different tissues?
- In most tissues (e.g. GI tract) noradrenaline causes vasoconstriction through the binding of a1 adrenoreceptors
- In skeletal muscles and coronary circulation noradrenaline causes vasoconstriction through the binding of a1 adrenoreceptors
27
What are the effects of noradrenaline on circulation of the blood?
- Noradrenaline binds to a1 adrenoreceptors causing vasoconstriction which increases TPR
- The increase in TPR increases BP by stimulating baroreceptors
- The stimulation of baroreceptors decreases heart rate
- Drop in heart rate causes cardiac output to drop
28
What are the effects of adrenaline on circulation?
- First TPR decreases due to vasodilation of skeletal muscles through the binding of B2-adrenoreceptors
- It will also bind to B1-adrenoreceptors on the heart causing an increase in heart rate and cardiac output
- There is no effect on blood pressure as when cardiac output goes up TPR goes down
29
How is Angiotensin II produced by the Renin-Angiotensin-Aldosterone system (RAAS)?
- A stimulus (e.g. low renal blood flow) is detected
- In response to this the kidney secretes Renin
- Renin is a protease which metabolises Angiotensinogen into angiotensin I
- The angiotensin I moves in circulation and as it passes the lungs it is converted into angiotensin II by Angiotensin Converting Enzyme (ACE)
30
What effect does angiotensin II have on the body?
- It increases thirst to improve blood volume and improve renal perfusion.
- It increases sympathetic drive from the medulla so more sympathetic tone to raise BP and decrease hydrostatic pressure at capillaries (less fluid squeezed out)
- It causes vasoconstriction which raises TPR
- It causes aldosterone release which increases the retention of NaCl in the kidneys so allows more water to be reabsorbed into the body which raises blood volume
31
How does vasopressin work in the body?
- The CVLM is able to stimulate vasopressin release from the pituitary.
- Stretch receptors in the left atrium send signals to the NTS in the medulla
- The NTS sends out inhibitory signals to the CVLM to prevent it from signalling vasopressin release.
- Dehydration or haemorrhage causes NTS inhibition to be switched off and so stimulate vasopressin release
- The hypothalamus can also cause vasopressin release when detecting an increase in osmolarity (i.e. dehydration or low blood volume)
- The vasopressin (ADH) released from the pituitary gland causes increased reabsorption of fluid by the kidneys and also causes vasoconstriction. (Both effects maintain blood pressure)
32
How is vasopressin released regulated?
- The NTS acts as a thermostat which sets the level at which CVLM is inhibited
33
How does atrial natriuretic peptide (ANP) work?
- Increased filling pressures stimulate stretch receptors causing atrial myocytes (muscle cells) to secrete ANP
- ANP act on ANP receptors on vascular smooth muscle cells to increase cGMP pathway
- As a result we experience vasodilation.
- The dilatation of renal arterioles increases GFR
- Na+ and water secretion by kidneys increases and blood volume decreases
