Nervous & Hormonal Control of Vascular Tone Flashcards
What is the role of intrinsic controls?
Regulate local blood flow to local organs / tissues
- important in regional hyperaemia
Name some Intrinsic controls for vascular tone
- myogenic response
- paracrine & auto-regulation
- agents, NO, PGs, H+, K+
- endothelin
- physical factors: temperature, stress etc.
What is the role of extrinsic controls?
Regulates TPR to control BP
Brain function selectively alters blood flow to organs according to need
e.g. during exercise, haemorrhage, thermoregulation
Give examples of Extrinsic controls of vascular tone
- parasympathetic & sympathetic sensory vasodilator
nerves - sympathetic vasoconstrictor nerves
- adrenaline, angiotensin II, ANP, ADH
What nerves are part of the extrinsic controls of vascular tone ?
Vasoconstrictors: noradrenaline
Vasodilators: Ach, NO
What hormones are part of the extrinsic controls of vascular tone?
Vasoconstrictors: adrenaline, angiotensin II, vasopressin
Vasodilators: Anti-natriuretic Peptide (ANP)
Describe the significance of the sympathetic vasoconstrictor system
most widespread and important extrinsic control
What is the significance of vascular tone?
Vascular tone controls TPR
What is vascular tone?
degree of constriction of a vessel compared to its maximally dilated state
How is vascular tone produced?
- Constant supply of sympathetic signals sends
noradrenaline to vessels, causing constriction - Background NO production by endothelial cells in
vessels, causes dilation
=> creates constant balance to allow control
What is the CVLM?
caudal ventrolateral medulla
What is the RVLM?
Rostral ventrolateral medulla
What is the function of the CVLM and RVLM?
RVLM and CVLM are centres in the brain that integrate signals to the sympathetic system, processing information from higher centres in the brain
How does the sympathetic vasoconstrictor system work?
- An axon moves to the spinal cord intermediolateral cell
column - Axon leaves spine from multiple areas onto post
ganglionic fibres which go to:
- β₁ adrenoceptors on the heart releasing NA causing
contractions - α₁ adrenoceptors release NA on arterioles causing
constriction - Adrenal glands (on top of kidneys) release adrenaline
into bloodstream.
α₁ adrenoceptors cause constriction, β₂ adrenoceptors
cause smooth muscle relaxation
Outline the mechanism of action of sympathetic vasoconstrictor nerves
- An action potential moves down the axon and arrives
at a varicosity - Depolarisation at the varicosity activates VGCCs
- Ingress of Ca2+ causes neurotransmitter release
(mainly noradrenaline) - NA diffuses to vascular smooth muscle cells where it
binds mainly α₁ - contraction, and some β₂ - relaxation
modulation of both responses - The NA is taken up again and recycled or broken
down
Adrenaline from adrenal glands is also released into circulation and can act on α₁ or β₂ receptors
What is a varicosity?
varix / varicose is an enlarged and torturous vein
What occurs at a varicosity?
Lots of modulation at a neurotransmitter level
- produces vasoconstriction or vasodilation as required
How can angiotensin II modulate NA release?
NA release can be modulated by angiotensin II which acts on AT1 receptors increasing NA release
How does NA modulate its own release?
NA can negatively feedback itself via α₂ receptors to limit its own release
How do metabolites regulate vasoconstriction?
K+, Histamine, adenosine & serotonin feedback and inhibit NA release causing vasodilation
Metabolites prevent vasoconstriction to maintain blood flow
How are sympathetic vasoconstrictor nerves regulated?
Sympathetic vasoconstrictor nerves are controlled by the brain stem
RVLM controlled by CVLM & hypothalamus
- provide central control of blood flow / blood pressure
Why is control of sympathetic vasoconstrictor nerves so significant?
Sympathetic vasoconstrictor nerves innervate most arterioles and veins of the body
Explain the role of noradrenaline on vascular tone
NA activates α₁ adrenoceptors on vascular smooth muscle cells causing vasoconstriction
What sets the vascular tone?
Tonic sympathetic activity (1 action potential per second)
What is the consequence of a decrease in sympathetic activity?
Produces vasodilation
- important principle in pharmacological treatment of cardiovascular disease e.g. hypertension
What are the main roles of the parasympathetic vasoconstrictor nerves?
- Contract resistance arterioles
- Distinct RVLM neurons (sympathetic) innervate different
tissues - Controls TPR
- Precapillary vasoconstriction
What is the effect of parasympathetic vasoconstrictors, contracting restriction arterioles?
produce vascular tone leading to vasodilation
- increased blood flow
- controls TPR
- Controls venous blood volume
What is the benefit of different RVLM neurons innervating different tissues?
Switches on vasoconstriction in some vessels and vasodilation in others
e.g. exercise increases sympathetic activity to GI (less blood flow) but reduced sympathetic nerve activity to skin (more blood flow to cool down)
How do parasympathetic vasoconstrictors control TPR?
maintain arterial blood pressure and blood flow to the brain and myocardium as Pa = CO x TPR
What is the function of precapillary vasoconstriction?
Leads to downstream capillary pressure drop = increased absorption of interstitial fluid into blood plasma to maintain blood volume (important in hypovolemia)
How do parasympathetic vasoconstrictors control venous blood volume?
Venoconstriction leads to decreased venous blood volume which increases venous return => increased SV via Starling’s Law
Are vasodilator nerves sympathetic or parasympathetic?
Mainly parasympathetic
Some sympathetic vasodilator nerves
Sensory Nociceptive C fibres are vasodilator fibres
Is it possible for tissues to contain both vasoconstrictor and vasodilator nerves?
A few specialised tissues contain vasodilator nerves as well as vasoconstrictor nerves
Normally occur in tissues controlling specific vascular beds
Vasodilator more prominent as vascular tone produced by sympathetic vasoconstrictor is inhibited
Where are the parasympathetic vasodilator nerves found?
Salivary glands - release ACh and VIP Pancreas & intestinal mucosa - release VIP Male genitalia (erectile tissue) - release NO
These tissues need high blood flow to maintain fluid secretion
What effect does Ach and VIP release cause?
Ach / VIP act on the endothelium to cause release of NO for vasodilation to occur
How does NO release on erectile tissue cause an erection?
NO released via parasympathetic nerves causing cGMP production leading to vasodilation
Sildenafil (viagra) enhances this effect of NO by inhibiting breakdown of cGMP by phosphodiesterase 5
Describe the effect of sympathetic vasodilator nerves
Skin (sudomotor fibres) - release Ach / VIP
- cause vasodilation via NO associated with sweating
- increased blood flow causes more sweat, allows heat
loss via skin
What are the overall effects of sympathetic vasoconstrictors on blood flow?
Sympathetic activity vasoconstriction
- reduces blood flow
- limits sweating
- limiting cooling
emotional stress in brain has some effect over these fibres
e.g. head, face, and upper chest involved in blushing
What are the roles of the sensory nociceptive fibres stimulated?
Sensory axon:
stimulated by trauma, infection etc.
Collateral axon:
release Substance P or CGRP
–> on mast cells releases histamine
–> acts on endothelium and vascular smooth muscle
both produce vasodilation called ‘flare’ in skin
What is the Lewis Triple response?
- local redness
- wheal
- flare
Name hormonal vasoconstrictors involved in circulation control
vasoconstrictors increasing BP are:
- adrenaline
- angiotensin II
- Vasopressin (ADH)
Give examples of the vasodilators involved in the control of circulation
- atrial natriuretic peptide (ANP)
decreases BP
What other hormones affect vasculature?
- insulin
- oestrogen
- relaxin
When is adrenaline (Epinephrine) secreted in circulation?
- exercise
- fight or flight response - increased sympathetic drive
- hypotension (baroreceptor reflex)
- hypoglycemia
Where is adrenaline secreted from in the body?
adrenaline is released form the adrenal medulla via the action of Ach on nAChR
What is the role of adrenaline?
Glucose metabolism
- skeletal muscle glycogenolysis, fat lipolysis
CVS
- Stimulation of heart rate and contractility during normal
exercise
- vasodilation of coronary & skeletal muscle arteries
What is the effect of NA/adrenaline on α₁ receptors?
- α₁ receptors stimulate Gq subunit
- activates phosholipase C
- PIP₂ -> IP₃ + DAG
- IP₃ binds to it’s receptor
- Ca2+ influx
- smooth muscle contraction
What effect does NA/adrenaline have when activating α₂ receptors?
- α₂ stimulate Gi pathway
- inhibits Ca2+ release - inhibits neurotransmitter release
- inhibits adenylate cyclase activity
- no smooth muscle contraction
What effects occur when Na/adrenaline bind to β receptors?
- β receptors stimulate Gs pathway
- increases adenylate cyclase activity
- converts ATP –> cAMP
- causes: - β₂ heart contraction
- β₂ smooth muscle relaxation; vasodilation
What is the effect of adrenaline on most tissues in the body e.g. skin, GI tract?
Vasoconstriction
What effect does noradrenaline have on most tissues of the body?
Vasoconstriction
What is the effect of adrenaline on skeletal muscle & coronary circulation?
Vasodilation
How does noradrenaline effect skeletal muscle and coronary circulation?
causes vasoconstriction
Which receptors does NA mainly act upon?
α₁ receptors to constrict vessels
Which receptors are most abundant in skeletal muscle and coronary arteries?
skeletal muscle & coronary arteries have more β₂ than α₂ adrenoceptors
Which receptors does adrenaline have a higher affinity for?
adrenaline has a higher affinity for β than α receptors
- mainly acts on β₂ receptors to dilate vessels
What are the effects of iv noradrenaline?
TPR increases due to vasoconstriction by α₁ receptors
- increasing BP
- stimulates baroreceptors - decreases HR
- drop in HR decreases CO
What is the effect of iv adrenaline?
Vasodilation caused by β₂ receptors
- TPR decreases
- CO increases
- increased CO maintains pressure (e.g. during exercise)
What is the effect of iv noradrenaline during sepsis?
During sepsis noradrenaline can be administered to raise BP
Outline the RAAS (renin-angiotensin-aldosterone system)
- Renin (protease) released due to low renal blood flow
and low NaCl load - Angiotensinogen, 453 amino acid precursor produced
in liver - angiotensinogen undergoes proteolysis via renin
- Angiotensin I (decapeptide) produced, travels to lungs
- ACE (angiotensin converting enzyme) cleaves off 2
amino acids –> (octapeptide) angiotensin II produced - angiotensin II circulates body producing several effects
What are the effects of angiotensin II around the body?
Vasoconstriction
- raises TPR, increasing BP
Central effects in brain
- increases thirst and sympathetic tone in vessels
- increasing BP to perfuse kidneys
Adrenal glands
- produces aldosterone (steroid)
- causes Na+ retention to increase [NaCl] in blood
- increases osmotic potential - fluid moves out of
interstitial space –> blood
- water reabsorption increases
What is diuresis?
the process of urine production
What is the pituitary gland?
organ producing hormones
How is a hypothalamus response stimulated?
Hypothalamus response is stimulated by increased osmolarity i.e. dehydration / low blood volume
What is the effect of vasopressin/ADH
- ADH released form pituitary gland
- vasoconstriction occurs, increasing renal water
reabsorption- both effects maintain BP by increasing blood volume
- stretch receptors in LA and aorta send signals to CNS
- causes firing in NTS
- NTS sends inhibitory signals to CVLM in brain stem
- CVLM stimulates pituitary to release ADH
- stretch of heart inhibits vasopressin (ADH) release
What is the effect of dehydration / haemorrhage on the RAAS system?
causes NTS inhibition to be switched off
CVLM stimulates vasopressin
What is the NTS?
Nucleustractus solitaris is the thermostat - stes the level at which CVLM is inhibited.
How is ANP secreted?
ANP is released by specialised atrial myocytes
When is ANP secreted?
When filling pressure increases stimulates stretch receptors - ANP secreted
What is the effect of ANP?
ANP binds to its receptors o vascular smooth muscle cells increasing cGMP pathway (like NO) causing vasodilation
- especially in arterioles leading to kidneys reducing BP
What are the main roles of the parasympathetic vasoconstrictor nerves?
- Contract resistance arterioles
- Distinct RVLM neurons (sympathetic) innervate different
tissues - Controls TPR
- Precapillary vasoconstriction
What is the effect of parasympathetic vasoconstrictors, contracting restriction arterioles?
produce vascular tone leading to vasodilation
- increased blood flow
- controls TPR
- Controls venous blood volume
What is the benefit of different RVLM neurons innervating different tissues?
Switches on vasoconstriction in some vessels and vasodilation in others
e.g. exercise increases sympathetic activity to GI (less blood flow) but reduced sympathetic nerve activity to skin (more blood flow to cool down)
How do parasympathetic vasoconstrictors control TPR?
maintain arterial blood pressure and blood flow to the brain and myocardium as Pa = CO x TPR
What is the function of precapillary vasoconstriction?
Leads to downstream capillary pressure drop = increased absorption of interstitial fluid into blood plasma to maintain blood volume (important in hypovolemia)
How do parasympathetic vasoconstrictors control venous blood volume?
Venoconstriction leads to decreased venous blood volume which increases venous return => increased SV via Starling’s Law
Are vasodilator nerves sympathetic or parasympathetic?
Mainly parasympathetic
Some sympathetic vasodilator nerves
Sensory Nociceptive C fibres are vasodilator fibres
Is it possible for tissues to contain both vasoconstrictor and vasodilator nerves?
A few specialised tissues contain vasodilator nerves as well as vasoconstrictor nerves
Normally occur in tissues controlling specific vascular beds
Vasodilator more prominent as vascular tone produced by sympathetic vasoconstrictor is inhibited
Where are the parasympathetic vasodilator nerves found?
Salivary glands - release ACh and VIP Pancreas & intestinal mucosa - release VIP Male genitalia (erectile tissue) - release NO
These tissues need high blood flow to maintain fluid secretion
What effect does Ach and VIP release cause?
Ach / VIP act on the endothelium to cause release of NO for vasodilation to occur
How does NO release on erectile tissue cause an erection?
NO released via parasympathetic nerves causing cGMP production leading to vasodilation
Sildenafil (viagra) enhances this effect of NO by inhibiting breakdown of cGMP by phosphodiesterase 5
Describe the effect of sympathetic vasodilator nerves
Skin (sudomotor fibres) - release Ach / VIP
- cause vasodilation via NO associated with sweating
- increased blood flow causes more sweat, allows heat
loss via skin
What are the overall effects of sympathetic vasoconstrictors on blood flow?
Sympathetic activity vasoconstriction
- reduces blood flow
- limits sweating
- limiting cooling
emotional stress in brain has some effect over these fibres
e.g. head, face, and upper chest involved in blushing
What are the roles of the sensory nociceptive fibres stimulated?
Sensory axon:
stimulated by trauma, infection etc.
Collateral axon:
release Substance P or CGRP
–> on mast cells releases histamine
–> acts on endothelium and vascular smooth muscle
both produce vasodilation called ‘flare’ in skin
What is the Lewis Triple response?
- local redness
- wheal
- flare
Name hormonal vasoconstrictors involved in circulation control
vasoconstrictors increasing BP are:
- adrenaline
- angiotensin II
- Vasopressin (ADH)
Give examples of the vasodilators involved in the control of circulation
- atrial natriuretic peptide (ANP)
decreases BP
What other hormones affect vasculature?
- insulin
- oestrogen
- relaxin
When is adrenaline (Epinephrine) secreted in circulation?
- exercise
- fight or flight response - increased sympathetic drive
- hypotension (baroreceptor reflex)
- hypoglycemia
Where is adrenaline secreted from in the body?
adrenaline is released form the adrenal medulla via the action of Ach on nAChR
What is the role of adrenaline?
Glucose metabolism
- skeletal muscle glycogenolysis, fat lipolysis
CVS
- Stimulation of heart rate and contractility during normal
exercise
- vasodilation of coronary & skeletal muscle arteries
What is the effect of NA/adrenaline on α₁ receptors?
- α₁ receptors stimulate Gq subunit
- activates phosholipase C
- PIP₂ -> IP₃ + DAG
- IP₃ binds to it’s receptor
- Ca2+ influx
- smooth muscle contraction
What effect does NA/adrenaline have when activating α₂ receptors?
- α₂ stimulate Gi pathway
- inhibits Ca2+ release - inhibits neurotransmitter release
- inhibits adenylate cyclase activity
- no smooth muscle contraction
What effects occur when Na/adrenaline bind to β receptors?
- β receptors stimulate Gs pathway
- increases adenylate cyclase activity
- converts ATP –> cAMP
- causes: - β₂ heart contraction
- β₂ smooth muscle relaxation; vasodilation
What is the effect of adrenaline on most tissues in the body e.g. skin, GI tract?
Vasoconstriction
What effect does noradrenaline have on most tissues of the body?
Vasoconstriction
What is the effect of adrenaline on skeletal muscle & coronary circulation?
Vasodilation
How does noradrenaline effect skeletal muscle and coronary circulation?
causes vasoconstriction
Which receptors does NA mainly act upon?
α₁ receptors to constrict vessels
Which receptors are most abundant in skeletal muscle and coronary arteries?
skeletal muscle & coronary arteries have more β₂ than α₂ adrenoceptors
Which receptors does adrenaline have a higher affinity for?
adrenaline has a higher affinity for β than α receptors
- mainly acts on β₂ receptors to dilate vessels
What are the effects of iv noradrenaline?
TPR increases due to vasoconstriction by α₁ receptors
- increasing BP
- stimulates baroreceptors - decreases HR
- drop in HR decreases CO
What is the effect of iv adrenaline?
Vasodilation caused by β₂ receptors
- TPR decreases
- CO increases
- increased CO maintains pressure (e.g. during exercise)
What is the effect of iv noradrenaline during sepsis?
During sepsis noradrenaline can be administered to raise BP
Outline the RAAS (renin-angiotensin-aldosterone system)
- Renin (protease) released due to low renal blood flow
and low NaCl load - Angiotensinogen, 453 amino acid precursor produced
in liver - angiotensinogen undergoes proteolysis via renin
- Angiotensin I (decapeptide) produced, travels to lungs
- ACE (angiotensin converting enzyme) cleaves off 2
amino acids –> (octapeptide) angiotensin II produced - angiotensin II circulates body producing several effects
What are the effects of angiotensin II around the body?
Vasoconstriction
- raises TPR, increasing BP
Central effects in brain
- increases thirst and sympathetic tone in vessels
- increasing BP to perfuse kidneys
Adrenal glands
- produces aldosterone (steroid)
- causes Na+ retention to increase [NaCl] in blood
- increases osmotic potential - fluid moves out of
interstitial space –> blood
- water reabsorption increases
What is diuresis?
the process of urine production
What is the pituitary gland?
organ producing hormones
How is a hypothalamus response stimulated?
Hypothalamus response is stimulated by increased osmolarity i.e. dehydration / low blood volume
What is the effect of vasopressin/ADH
- ADH released form pituitary gland
- vasoconstriction occurs, increasing renal water
reabsorption- both effects maintain BP by increasing blood volume
- stretch receptors in LA and aorta send signals to CNS
- causes firing in NTS
- NTS sends inhibitory signals to CVLM in brain stem
- CVLM stimulates pituitary to release ADH
- stretch of heart inhibits vasopressin (ADH) release
What is the effect of dehydration / haemorrhage on the RAAS system?
causes NTS inhibition to be switched off
CVLM stimulates vasopressin
What is the NTS?
Nucleustractus solitaris is the thermostat - stes the level at which CVLM is inhibited.
How is ANP secreted?
ANP is released by specialised atrial myocytes
When is ANP secreted?
When filling pressure increases stimulates stretch receptors - ANP secreted
What is the effect of ANP?
ANP binds to its receptors o vascular smooth muscle cells increasing cGMP pathway (like NO) causing vasodilation
- especially in arterioles leading to kidneys reducing BP
What is the effect of blood volume is too high?
Systemic vasodilation opposes the cation of noradrenaline, RAAS and ADH when blood volume is too high
Describe the effect of renal afferent arteriole dilation
Dilation of the renal afferent arteriole increases GFR
Na+ and H₂O excretion via kidneys increases
Blood volume reduces
Decreases release / action of aldosterone, ADH and renin
How is glomerular filtration rate (GFR) increased?
Increasing the blood flow to the kidneys increases GFR
