Nervous & Hormonal Control of Vascular Tone Flashcards
What is local (vascular) control
Regulate local blood flow to organs/tissues
Important – regional hyperaemia (increase in blood flow)
Vasodilators - inflammation, local metabolites such as Nitric oxide, Prostaglandins, Endothelin, K+, H+
What is extrinsic (vascular) control
Brain function selectivity alters blood flow to organs according to need
Nerves
Vasoconstrictors - noradrenaline vasodilators - acetylcholine, nitric oxide
Hormones
Vasoconstrictor - adrenaline, angiotensin II vasodilators - anti-natriuretic peptide (ANP)
Give examples of intrinsic control
Myogenic response - found in arteries/arterioles
Paracrine and autocrine - found in arteries/arterioles and veins/venules
Physical factors - Temperature, Shear stress - found in arteries/arterioles and veins/venules
Give examples of extrinsic control
Parasympathetic, sympathetic & sensory vasodilator nerves - found in arteries/arterioles
Sympathetic vasoconstrictor nerves - found in arteries/arterioles and veins/venules
Adrenaline, Angiotensin II, Vasopressin, Atrial natriuretic peptide - found in arteries/anterioles and veins/venules
Describe the sympathetic vasoconstrictor system
- Medulla oblongata coordinates certain reflexes - the brain also processes information and sends signals to the brain hence it is both a reflex and coordinated action
- There are main excitatory nerves (sympathetic preganglionic fibres) in the spinal cord that emerge from the spinal cord between T1 and L2 (intermediolateral cell column)
- These then form sympathetic ganglia with postganglionic sympathetic fibres - preganglia releases acetylcholine which binds to nicotinic receptors on the postganglionic fibre
- These then innervate vessels, the heart and adrenal glands
- At the heart noradrenaline is released which binds to beta 1 receptors which increase adenylate cyclase increasing formation of cAMP for ATP which increases protein kinase activity which increases [Ca2+] and increases heart rate/stroke volume because of this
- In the vessels the noradrenaline binds to an alpha 1 receptor which increases activity of phospholipase C which cleaves PIP2 into IP3 and DAG which causes constriction of the vessels
- The adrenal medulla is also able to produce adrenaline which can bind to beta 2 receptors which can lead to dilation/relaxation - adenylate cyclase activity is reduced so less ATP forms cAMP so protein kinase A activity decreases - adrenaline can also bind to alpha 1 receptors and cause constriction in some vessels
Describe how sympathetic vasoconstrictor nerves interact with smooth muscle
- An action potential moves down the axon and arrive at a varicosity
- Depolarisation at the varicosity activating voltage gated Ca2+ channel
- 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 dilation
- 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
Describe how varicosities (swellings) function in more detail
- 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. feedback and inhibit NA release
- NA can also negatively feedback 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
How are sympathetic vasoconstrictor nerves controlled by the brainstem
- Rostral ventrolateral medulla (RVLM) – this is controlled by other areas such as the caudal ventrolateral medulla (CVLM) & hypothalamus.
- Provides central control of blood flow & blood pressure.
How do sympathetic vasoconstrictor nerves innervate most arterioles & veins
- NA activates a1-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 main roles of sympathetic vasoconstrictor nerves
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Distinct sympathetic pathways innervate different tissues
Switching on vasoconstriction in some vessels and off in other vessels (producing vasodilation) eg. During exercise increased sympathetic nerve stimulation to GI (less blood flow), reduces sympathetic nerve stimulation to skin (more blood flow, to assist heat loss) -
Control resistance arterioles
Produces vascular tone allows vasodilatation/vasoconstriction controlling TPR. Maintains arterial blood pressure and blood flow to brain myocardium & kidney etc. -
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 venous blood volume
Venoconstriction leads to decreased venous blood volume increasing venous return, this increases stroke volume via Starling’s law and so increases cardiac output
When does vasodilation usually occur
Vasodilatation usually occurs when 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
Describe how specific vasodilator nerves work
Specific vasodilator nerves are mainly parasympathetic
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 can also cause contraction of smooth muscle via M2 and M3 receptors but usually less predominant than the NO effect
Cerebral arteries appear to have M5 muscarinic receptors that vasodilate in response to ACh
Give examples of parasympathetic vasodilators
- 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 tact on endothelium & 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
Give examples of sympathetic vasodilators
- Skin (sudomotor fibres) release Ach, VIP causing vasodilatation via NO associated with sweating – increased blood flow causes more sweat and also allows heat loss via skin
- Sympathetic activity vasoconstriction would only 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
Describe the action of sensory (nociceptive C fibres) vasodilator fibres (in terms of trauma to the skin)
- Stimulation of sensory axon reflex (C-fibres) by trauma, infection etc. Release substance P or calcitonin gene-related peptide (CGRP)
- Act on mast cells to release histamine endothelium and vascular smooth muscle. Both produce vasodilatation called ‘flare’ in skin
- Inflammation is part of the Lewis triple response:
1. Redness, caused by capillary vasodilation
2. Flare, a redness in the surrounding area due to arteriolar dilation mediated by axon reflex
3. Wheal, exudation of extracellular fluid from capillaries and venules - Increased delivery of immune cells & antibodies to site of damage to deal with invading pathogens
