Nervous and hormonal control of vascular tone Flashcards
What does intrinsic control regulate?
Why is it important?
Regulate local blood flow to organs/tissues
Important – regional hyperaemia (increase in blood flow)
Give some examples of things that provide intrinsic control
Vasoconstrictors eg myogenic response
Vasodilalators eg inflammation,
local metabolites
Nitric oxide, Prostaglandins
Endothelin, K+, H+
What does extrinsic control regulate
Regulate TPR to control blood pressure
Give some examples of extrinsic control
Brain function selectivity alters blood flow to organs according to need eg. during exercise, thermoregulation etc.
Nerves
vasoconstrictors - eg. noradrenaline
vasodilators - eg. acetylcholine, nitric oxide
Hormones
vasoconstrictor – eg. adrenaline, angiotensin II, vasopressin
vasodilators – eg. anti-natriuretic peptide (ANP)
Describe the sympathetic vasoconstrictor system (pathway involved)
On image
Describe the pathway that causes vasoconstriction
An action potential moves down the axon and arrive at a varicosity.
Depolarisation at the varicosity activating voltage gated Ca2+ channels.
Ingress of calcium causes release of neurotransmitters - mainly noradrenaline.
NA diffuses to the vascular smooth muscle cells where it binds mainly α1 – contraction; some α2 – contraction and β2 – relaxation. Modulation of responses in both constriction and dilatation.
The noradrenaline is then taken up again and recycled or broken down.
Adrenaline from the adrenals and released into the circulation can also act at α1 or β2 receptors.
How can release of noradrenaline be modulated?
How can noradrenaline also regulate itself via negative feedback?
Release of NA can be modulated by Angiotensin II acting on AT1 receptor increasing NA release.
Metabolites prevent vasoconstriction to maintain blood flow; K+, adenosine, histamine & serotonin etc feed back and inhibit NA release.
NA can also negatively feed back itself via α2 receptors to limit its own release.
Lots of modulation occurring at the neurotransmitter level at the varicosity. It produces vasoconstriction and vasodilation as required.
On image
What are sympathetic vasoconstrictor nerves controlled by?
How is it controlled by the brainstem?
Controlled by brainstem
Rostral ventrolateral medulla (RVLM) – this is controlled by other areas such as…
Caudal ventrolateral medulla (CVLM) & hypothalamus.
Provides central control of blood flow & blood pressure.
Innervate most arterioles & veins
NA activates 1-adrenoceptors on vascular smooth muscle cells causing vasoconstriction.
Sympathetic nerve activity is tonic
(1 action potential per second)
Tonic sympathetic activity sets vascular tone.
Decrease in sympathetic activity producing vasodilatation is an important principle in pharmacological treatment of cardiovascular disease, eg. Hypertension.
What are the 4 main roles of sympathetic vasoconstrictor nerves?
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).
Control venous blood volume:
Venoconstriction leads to decreased venous blood volume increasing venous return, this increases stroke volume via Starling’s law.
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).
Contract resistance arterioles:
Produces vascular tone allows vasodilatation/increased blood flow to occur, controls TPR.
Maintains arterial blood pressure and blood flow to brain myocardium & kidney etc
Describe how vasodilatation usually occurs as vascular tone produced by sympathetic vasoconstrictor nerves is inhibited.
A few specialised tissues contain vasodilator nerves, as well as vasoconstrictor nerves.
Normally these have an specific function controlling a specific vascular bed rather than global functions.
A few sympathetic vasodilator nerves exist
eg. Sensory (nociceptive C fibres) vasodilator fibres
How are Specific vasodilator nerves parasympathetic?
How does the parasympathetic nervous system cause vasodilation?
What does activation of M3 receptors cause?
What do the activation of M2 and M3 cause?
Where are M5 receptors found and what do they cause?
Some blood vessels are innervated by parasympathetic cholinergic fibres (eg. coronary vessels). These release acetylcholine (Ach) which binds to muscarinic receptors on the smooth muscle and/or endothelium.
M3 receptors located on the vascular endothelium can coupled to the formation of nitric oxide (NO) causing vasodilation.
However, ACh also causes contraction through smooth muscle M2 and M3 receptors.
Cerebral arteries appear to have M5muscarinic receptors that produce vasodilation in response to ACh.
How do sympathetic sudomotor vasodilator fibres work?
In terms of body temperature, what does vasodilation and constriction cause?
Skin (sudomotor fibres) – release acetylcholine (Ach) and vasoactive intestinal peptide (VI) causing vasodilatation via NO associated routes.
Increased blood flow causes more sweat and also allows heat loss via skin.
Sympathetic activity vasoconstriction would reduce blood flow, limit sweat production and limit cooling.
Emotional centres in brain have some control over these fibres, head, face, upper chest, involved in blushing.
How do parasympathetic salivary glands, pancreas and intestinal mucosa and male genitalia function
Salivary glands – release acetylcholine (Ach) vasoactive intestinal peptide (VIP)
Pancreas & intestinal mucosa – release VIP
Both these tissues need high blood flow to maintain fluid secretion.
Ach/VIP act on endothelium to cause release of nitric oxide (NO) - vasodilatation
Male genitalia (erectile tissue) – release NO Release of NO by parasympathetic nerves causes production of cGMP which leads to vasodilatation.
Sildenafil (Viagra) enhances this effect of NO by inhibiting the breakdown of cGMP by phosophodiesterase-5.
Where adrenaline produced?
What does it cause?
Adrenaline is released from adrenal medulla – via action of acetylcholine on nicotinic receptors during…
Exercise
Flight-Fight-Fear response (increase sympathetic drive)
Hypotension (baroreceptor reflex)
Hypoglycaemia
What are the main roles of adrenaline?
Main roles – metabolic and CVS effects Glucose mobilisation (skeletal muscle glycogenolysis, fat lipolysis)
Stimulation of heart rate & contractility during normal exercise
Vasodilatation of coronary and skeletal muscle arteries
