Nervous and Hormonal Control of Vascular Tone Flashcards
Give examples of three molecules that cause vasoconstriction
- Adrenalin
- Angiotensin II
- Vasopressin
What might trigger vasoconstriction?
Low blood pressure
Where is ANP (atrial natriuretic peptide) secreted from?
Specialised atrial myocytes
What is the effect of ANP on vascular tone?
Vasodilation
- Opposes action of adrenalin, vasopressin etc.
What might stimulate the release of ANP?
- Stimulation of stretch receptors
- This is triggered by increased atrial filling pressure/ increased blood volume
What receptors does ANP act on?
The receptors on vascular smooth muscle e.g arterioles, blood vessels etc.
Where are the ANP receptors in the kidneys found?
Afferent arterioles
Suggest the effect of stimulation of the kidney ANP receptors.
- Increased volume of blood filtered by kidney (i.e greater GFR)
- Increased filtration by the kidney
- Reduced blood volume
Where is vasopressin synthesised and released from?
SYNTHESISED - hypothalamus
RELEASED FROM - vesicles in posterior pituitary
What are the two ways in which vasopressin maintains blood pressure and increase blood volume?
- Vasoconstriction
- Reabsorption of fluid from kidney (reduced filtration of blood)
Define diuresis
Filtration of blood at the kidneys
- Vasopressin opposes this action
Outline the steps involved in the release of vasopressin.
- Stretch receptors in the aortic arch and on the left atrium continually send signals to an area of the medulla - the nucleus tractus solitarius (NTS).
- The NTS then sends an inhibitory signal to another area of the medulla - the caudal ventrolateral medulla (CVLM).
- The CVLM sends signals to the posterior pituitary to stimulate the release of ADH
How is vasopressin release inhibited when blood volume is low/pressure is normal?
- Stretching causes signal to be sent to NTS
- Inhibitory signal sent to CVLM
- Reduced release of vasopressin
How is stretching affected when blood pressure/blood volume is reduced?
Stretching is reduced
What is the consequence of reduced stretching of the heart?
- Reduced signal sent to NTS
- Reduced inhibitory signal sent to CVLM
- Increased CVLM signal to hypothalamus
- Vasopressin is released
What are two other ways in which vasopressin may be released?
- Detection of increased osmolarity of blood e.g due to dehydration
- Also stimulated by angiotensin II release
What stimuli may cause the release of renin from kidneys?
- Decrease in renal blood flow
- Reduction in amount of Na+ being filtered really
- Increased sympathetic nervous system activity
What is the purpose of renin?
- Protease enzyme
- Cleaves precursor, angiotensinogen to active molecule angiotensin I
Where is angiotensinogen found and produced?
PRODUCED - in liver
FOUND - in circulation
Compare the amino acid length of angiotensinogen to that of angiotensin I.
ANGIOTENSINOGEN - 453 amino acids
ANGIOTENSIN I - 10 amino acids
When is angiotensin I converted to angiotensin II?
As angiotensin I passes through the lungs
How long is angiotensin II?
8 amino acids
Which protease enzyme catalyses the conversion of angiotensin I to angiotensin II?
ACE (angiotensin converting enzyme)
Why do angiotensin II concentrations rise very rapidly?
Each molecule of renin and ACE can catalyse the cleavage of a large number of substrates
What are the three major effects of angiotensin II?
- Acts as a vasoconstrictor and increases TPR
- Stimulates sympathetic nervous activity
- Stimulates aldosterone release
What are the effects of increasing TPR and sympathetic nervous activity?
Greater blood pressure
What is the effect of releasing aldosterone?
- Greater reabsorption of sodium ions and greater water retention
- Increases blood volume
Angiotensin II also acts on the hypothalamus. Suggest a possible effect.
Triggering vasopressin release
How might an intravenous injection of adrenalin influence heart rate and cardiac output?
- Adrenalin has a high affinity for β-receptors
- Binding to β-receptors causes an increase in heart rate and therefore, increase in cardiac output
How might an intravenous injection of adrenalin influence TPR?
- Binding to skeletal muscle β2-receptors causes vasodilation
- May activate some α1-receptors causing vasoconstriction (this response is lower - due to higher affinity for β-receptors)
- TPR goes down
What is the overall effect on blood pressure by an intravenous injection of adrenalin?
Very little change in blood pressure
How might an intravenous injection of noradrenaline influence TPR and blood pressure?
- High affinity for α-receptors
- Binding to α1-receptors causes vasoconstriction
- TPR increases and therefore blood pressure rises
How might an intravenous injection of noradrenaline influence heart rate and cardiac output?
- High BP stimulates baroreceptors
- Reduced sympathetic signals to β1-receptors
- Decrease in heart rate, therefore decrease in cardiac output
When might an intravenous injection of noradrenaline be administered clinically?
- During hypotension (reduction in blood pressure)
- To raise blood pressure without damaging the heart
In most tissues which receptors mediate vasoconstriction and vasodilation?
VASOCONSTRICTION - α1adrenoreceptors
VASODILATION - β2 adrenoreceptors
In skeletal muscle, adrenaline causes vasodilation and noradrenaline causes vasoconstriction. Suggest a reason for this difference.
- Difference in receptor affinity
- Adrenaline has higher affinity for β2-receptors and so causes vasodilation
- Noradrenaline has higher affinity for α1-receptors and so cause vasoconstriction
Where is adrenaline released from?
Adrenal medulla
Outline how adrenaline is released from the medulla.
- Released in response to sympathetic nervous system through splanchnic nerves passing to adrenal glands
- ACh released at preganglionic fibres and acts on nicotinic ACh receptors. This stimulates adrenaline release
Outline the effects of adrenaline (along with which receptor is stimulated)
- Vasodilation of coronary and skeletal muscle arteries (β2)
- Stimulation of heart rate and contractility (β1)
- Glucose metabolism (e.g glycogenolysis) (β3)
What are the purpose of sensory vasodilator fibres/C-fibres?
Convey pain signals to the brain when stimulated by trauma
What are the main effects of sensory vasodilator fibres?
- Stimulation up the dorsal root ganglia and up spinal cord
- Stimulation of axon collaterals
What would be the effect of stimulating axon collaterals?
- Release of Substance P which cause vasodilation of blood vessels, degranulation of mast cells
- OVERALL EFFECT: heavy vasodilation close to site of trauma
Outline the purpose of the inflammatory response with regards to trauma
Increased delivery of immune cells to site of trauma to kill invading pathogens
The Lewis Triple effect lists three effects that occur due to vasodilation.
Outline these effects.
- Local redness due to vasodilation
- ‘Flare’ - further redness in surrounding area due to arteriole dilation
- Wheals - exudation of extracellular fluid from capillaries/venules
Why is vasodilation important for the GI tract and salivary glands?
- High blood flow needed to maintain fluid secretion - so both GI tract and glands release ACh, VIP etc.
- Blood flow for secretory areas maintained by ACh
- VIP increases gut secretions and motility
How does NO induce vasodilation?
Causes conversion of GTP to cGMP which causes vasodilation
What is the importance of having sympathetic vasodilators during thermoregulation?
- Release ACh, VIP to cause vasodilation and increase blood flow
- Greater blood flow means greater heat loss and greater sweating at high temperatures
- Vasoconstriction would limit cooling and sweat production
TRUE OR FALSE - Specific vasodilator nerves are dominantly sympathetic
FALSE
- There are only a few sympathetic vasodilator nerves
- Most are parasympathetic/cholinergic fibres
Name and outline a possible mechanism for vasodilation caused by the parasympathetic nervous system
- Parasympathetic fibres release ACh which bind to M3 receptors on smooth muscle/endothelium
- Activation of these receptors cause formation of NO
- This causes conversion of GTP to cGMP
RESULT: Vasodilation
A patient has a cholinomimetic drug administered. This causes a mixture of both vasoconstriction an vasodilation. Suggest why.
CHOLINOMIMETIC DRUGS - drugs which mimic the action of acetylcholine
- ACh can also cause vasoconstriction e.g through M2 receptors
- ACh also causes vasodilation through M3 receptors
Suggest a possible effect of endothelial damage on vascular tone.
- Disrupted release of NO
- Reduced vasodilation/increased vasoconstriction
What causes vasodilation of cerebral arteries?
- Activation of M5 receptors by ACh
How does venoconstriction influence cardiac output?
- Decreased venous blood volume
- Greater venous return
- Greater stretching and greater force of contraction (through Starling’s Law)
- Greater cardiac output
What is the effect of vasoconstriction of arterioles?
- Reduced blood pressure downstream
- Reduced hydrostatic pressure at capillaries
- Greater reabsorption of fluid from interstitial fluid
What is the effect of changing the vascular tone of arterioles?
- Vasoconstriction will increase TPR - vasodilation will do the opposite
- Arterial blood flow to areas such as the brain and myocardium is maintained
Describe the effect of having multiple sympathetic pathways on vasoconstriction.
- Allows blood flow to be directed where it is needed
- Allows blood pressure and flow to be tailored to specific situations
- During hot conditions, reduced stimulation to skin - greater blood flow, greater heat loss
What is the effect of the RVLM?
- Works with other centres such as the CVLM to coordinate control of the CVS and regulate activity of preganglionic fibres
- Uses nervous information to produce sympathetic-mediated responses to control blood pressure and flow based on needs
Outline the general effect that sympathetic stimulation has on the blood vessels
Binding of noradrenaline to α1adrenoreceptors
How can vasodilation be caused through the sympathetic nervous system?
- Reduce sympathetic stimulation
- Reduce vascular tone. RESULT: vasodilation
Give a clinical example of where a decrease in sympathetic activity is beneficial
AMLODIPINE - used to treat hypertension
- Causes reduced vascular tone
- Causes greater vasodilation
How is noradrenaline released from the nerve?
- Action potential stimulates opening of VGCCs
- Increased calcium influx
- Greater intracellular [Ca2+] which triggers release of vesicles containing noradrenaline
Give an example of a stimulus that would increase noradrenaline release.
- Stimulated by binding of angiotensin II to AT1 receptor
Give an example of a stimulus that would decrease noradrenaline release.
- Binding of metabolites such as H+
- Binding of vasodilators such as histamines
What is the effect of increasing noradrenaline release?
What is the effect of decreasing noradrenaline release?
INCREASE - increase in vascular tone and vasoconstriction
DECREASE - vasodilation
How can noradrenaline limit its own release?
- Important when the concentration of noradrenaline is very high
- Noradrenaline binds to α2 adrenoreceptors
- This inhibits adenylate cyclase
- This prevents action of PKA
- Reduced phosphorylation of calcium ion channels
- Reduced release of noradrenaline
Where is noradrenaline released from?
Swellings in sympathetic vasoconstrictor nerves
- These swellings are called ‘varicosities’
Outline how noradrenaline causes vasoconstriction.
- Action potential moves down axon and arrives at varicosity
- Varicosity becomes depolarised and VGCCs open
- Increase in intracellular [Ca2+] which causes noradrenaline release
- Binds to α1 adrenoreceptors on vascular smooth muscle and causes vasoconstriction
- Noradrenaline is then taken up again or hydrolysed
What is the effect of having multiple varicosities?
Greater area of smooth muscle affected
Where do the preganglionic fibres originate in the sympathetic nervous system?
The IML of the spinal cord
What do the preganglionic fibres travel to?
- Ganglia - synapse with a postganglionic fibre
What occurs at the ganglia?
Release of ACh which binds to nicotinic ACh receptors
Noradrenaline is released by most postsynaptic neurones.
Outline two of its effects.
VASOCONSTRICTION - binding to α1 adrenoreceptors
VASODILATION OF SOME BLOOD VESSELS - binding to β2 adrenoreceptors
What is the effect of sympathetic innervation of the adrenal medulla?
Triggers adrenalin release which can activate α1 and β2 receptors
What is the difference between arterioles and veins?
ARTERIOLES - resistance vessels - affect TPR
VEINS - capacitance vessels - hold onto a reservoir of blood that can be mobilised when needed
What is the difference between intrinsic and extrinsic control of blood flow?
INTRINSIC - local control of blood flow
EXTRINSIC - dependent on external sources such as hormones
Give examples of intrinsic controls of blood flow.
- Physical factors e.g temperature and stress
- Local metabolites e.g histamines, endothelins
Give examples of extrinsic controls of blood flow.
- Hormones
- Innervation by vasodilator and vasoconstrictor nerves
