nervous and hormonal control of vascular tone Flashcards
What are the 2 types of vascular control?
- Local control
○ Myogenic responses
○ Paracrine and autoregulation agents
○ Physical factors
2. Extrinsic control ○ Parasympathetic ○ Sympathetic ○ Sensory vasodilator nerves ○ Sympathetic vasoconstrictor nerves
Others
What is the importance of intrinsic controls?
Regulates local blood flow to organs and tissues
aka regional hyperaemia
What is the importance of extrinsic controls?
- Regulates TPR to control blood pressure
- Brain function selectively alters blood flow to organs/tissues where needed
For example more blood flow is required to muscles during exercise - Nerves:
• Vasodilator (acetylcholine + nitric oxide)
• Vasoconstrictor (noradrenaline) - Hormones
• Vasodilator (ANP)
- Vasoconstrictor (vasopressin + adrenaline + angiotensin II)
What is the most widespread and important extrinsic control?
Sympathetic vasoconstrictor system
Describe how the sympathetic innervation of arterioles leads to NA release and explain the different outcomes
- An action potential moves down the axon and arrives at the varicosity; innervating the adventitia
- Depolarisation occurs at varicosity, activating the voltage gated calcium channels
- This causes an influx of calcium ions
- Influx of Ca2+ = release of neurotransmitter (noradrenaline-NA)
- NA diffuses to vascular smooth muscle, and binds to:
• Mainly alpha-1 = contraction
• Some alpha-2 = contraction
• Some beta-2 = relaxation
These responses are modulated during vasoconstriction and vasodilation - NA is then taken back up again and is either recycled OR broken down
Adrenaline that is released from the adrenal glands and released into the bloodstream can also act as alpha-1 or beta-2 receptors
Describe what happens at varicosity in detail
• Release of NA can be modulated by angiotensin II (+)
• Angiotensin II binds to AT1 receptors = increase in cAMP = increases calcium influx via voltage gated calcium channels = more NA released = increased vasoconstriction
• Some metabolites prevent vasoconstriction by negatively regulating cAMP = less NA release = less vasoconstriction = more blood flow
These metabolites include:
1. Serotonin
2. K+
3. Adenosine
4. Histamine
• NA can also inhibit it’s own release by binding to alpha-2 receptors
More NA = more vasoconstriction = less blood flow
Less NA = less vasoconstriction = more blood flow
What are the sympathetic vasoconstrictor nerves controlled by?
Controlled by the brainstem
Rostral ventrolateral medulla (RVLM) – this is controlled by other areas, Caudal ventrolateral medulla (CVLM) & hypothalamus.
Provides central control of blood flow/blood pressure
What causes arteriole and venues vasoconstriction?
NA binds to alpha-1 receptors on vascular smooth muscle causing vasoconstriction
Why is a decrease in sympathetic activity important?
Decrease in sympathetic activity producing vasodilatation is an important principle in pharmacological treatment
of cardiovascular disease, eg. Hypertension.
What are the main roles of the sympathetic vasoconstrictor nerves
- Contract resistance arterioles
Produces vascular tone allows vasodilatation/increased blood flow to occur, controls TPR.- Distinct RVLM neurones-sympathetic pathways innervate different tissues
Switching on vasoconstriction in some vessels and off in other vessels (producing vasodilation)
eg. exercise, increased sympathetic nerve stimulation to GI (less blood flow), reduce sympathetic nerve stimulation to skin (more blood flow, cool down). - Pre-capillary vasoconstriction
Leads to downstream capillary pressure drop so increased absorption of interstitial fluid into blood plasma to maintain blood volume (important in hypovolemia). - Control TPR
Maintains arterial blood pressure and blood flow to brain/myocardium since Pa = CO x TPR - Controls venous blood volume
Venoconstriction leads to decreased venous blood volume increasing venous return, this increases stroke volume via Starling’s law.
- Distinct RVLM neurones-sympathetic pathways innervate different tissues
What is an example of a sympathetic vasodilator nerve?
Sensory vasodilator fibres (nociceptive C fibres)
However, body mainly uses parasympathetic vasodilator nerves
Where are the parasympathetic vasodilator nerves founds?
- Salivary glands
Release Ach and VIP- Pancreas and intestinal mucosa
Release VIP
Both these tissues need high blood flow to maintain fluid secretion - Male genitalia
Release NO via parasympathetic nerves = production of cGMP = vasodilation
- Pancreas and intestinal mucosa
What is Sildenafil and how does it affect parasympathetic vasodilator nerves?
Viagra
Enhances the effect of NO on erectile tissues by inhibiting breakdown of cGMP
Where are the sympathetic vasodilator nerves found and how do they work?
Skin
Release Ach and VIP = vasodilation via NO = increases blood flow = increase sweat= heat loss via skin
What is the effect of the sympathetic vasoconstrictors on the skin?
Reduce blood flow = less sweat = limits heat loss
Emotional centres in the brain have control over the structures involved in blushing
Describe the effect of stimulation of sensory (nociceptive C fibres) vasodilator fibres
The stimulation of the sensory axon reflex occurs by trauma and infection
They release a substance called substance P or calcitonin gene related peptide (CGRP)
This acts on mast cells to release histamine. It also acts on the endothelium and vascular smooth muscle
Both histamine and CGRP produce vasodilation = flare on skin
What do sensory vasodilator fibres release and act on?
Release: substance P + CGRP
Act on: mast cells + endothelium + vascular smooth muscle
What is the effect of histamine or CGRP release from the sensory vasodilator fibres?
Flare on skin
What is the lewis triple response?
- Local redness
- Wheal
- Flare
Name some hormones that affect the control of circulation
1. Vasoconstrictors • Adrenaline • Angiotensin II • Vasopressin (ADH) 2. Vasodilator • Atrial natriuretic peptide (ANP) 3. Others • Insulin • Oestrogen • Relaxin
Describe the release of adrenaline aka epinephrine
Adrenaline is released from the adrenal medulla via the action of Ach on nicotinic cholinergic receptors during:
Exercise
Fight or flight response (> sympathetic drive)
Hypotension (baroreflex receptor)
Hypoglycaemia
Describe the main roles of adrenaline release
Metabolic and CVS effects
• Glucose metabolism (skeletal muscle glycogenolysis, fat lipolysis)
• Stimulation of heart rate and contractility during normal exercise
• Vasodilation of coronary and skeletal muscle artery
Describe the effect of adrenaline and NA on most tissues such as GI tract and skin
NA = vasoconstriction Adrenaline = vasoconstriction
Describe the effect of adrenaline and NA on skeletal muscle and coronary circulation
NA= vasoconstriction Adrenaline= vasodilation
What receptor does adrenaline act on to dilate vessels
Adrenaline mainly acts on B2 receptors to dilate vessels
What receptor does NA act on to constrict vessels
NA acts mainly on A1 receptors to constrict vessels
What are the main receptors found on coronary arteries and skeletal muscle?
Beta 2 receptors
What does stimulation of alpha1-Gq receptor result in?
Smooth muscle contraction
What does stimulation of alpha1-Gi receptors result in?
Smooth muscle contraction
What does inhibition of alpha1-Gi receptors result in?
Inhibition of neurotransmitter release
What does the stimulation of B-Gs result in?
B1= heart contraction B2= smooth muscle relaxation = vasodilation
Describe the effect of IV adrenaline on circulation
CO: increases
TPR: decreases
BP: not much effect
When given adrenaline, the heart rate increases. The CO increases HOWEVER because the TPR decreases (due to B2 receptor stimulation) there is not much effect on BP
Describe the effect of IV NA on circulation
CO: decreases TPR: increases BP: increases HR: decreases When given NA, there is a big increase in TPR (due to A1 receptor stimulation) which causes an increase in BP. Increased BP stimulates the baroreceptor reflex to decrease heart rate
What is meant by RAAS?
Renin-angiotensin-aldosterone system
Describe how RAAS responds to lowered blood pressure
Lowered BP = renin release from kidney via JGA (juxtaglomerular apparatus)
1. Renin triggers proteolysis of angiotensinogen —> angiotensin I
2. Lung releases ACE (angiotensin converting enzyme) converting angiotensin I—> angiotensin II
3. Angiotensin II triggers several responses which all lead to an increased blood pressure
• Angiotensin II directly causes vasoconstriction = raises TPR = increase in BP
• Angiotensin II causes the adrenal cortex to release a steroid hormone called aldosterone which increases kidney water retention via Na+ movement = raise in blood volume = increases BP
Angiotensin II also directly increases the body’s sympathetic response = increase BP
What type of hormone is vasopressin?
ADH
Anti diuretic hormone
STOPS YOU PEEING
How does the body respond to low blood volume (ie- low BP)
• Dehydration or low blood volume stimulated the hypothalamus response to release CVLM
• CVLM cause magnocellular neurons in SON and PVN to release vasopressin from the posterior pituitary gland
Vasopressin release = acts as ADH + causes vasoconstriction = increases BP
How does the body respond to high blood volume (ie- high BP)
• Left atrial receptors and arterial baroreceptors send signals to the NTS in the brainstem
• NTS negatively regulates the release of CVLM by sending negative inhibitory signals
Inhibition of CVL = no ADH release = more urine released to lower blood volume = lowers BP
What is ANP and what releases it?
Anti natriuretic peptide released by specialised atrial myocytes
Secreted by increased filling pressures which stimulate stretch receptors (left atrial receptors and arterial baroreceptors)
Describe the mechanism of action of ANP
ANP act as receptors on vascular smooth muscle for things such as NO = increasing cGMP pathway = vasodilation
Describe how ANP opposes RAAS, NA, and ADH
ANP = dilation of renal arterioles = increase in GFR
This means that sodium and water excretion is increases = blood volume decreases
Decrease in blood volume opposes action of NA, RAAS and ADH
