Nervous And Hormonal Control Of Vascular Tone Flashcards
What are the two types of vascular control (including examples of each)?
LOCAL CONTROL:
- myogenic response
- paracrine and autoregulation agents (NO, PGs, Endothelin, K+, H+)
- physical factors (temperature, shear stress)
EXTRINSIC CONTROL:
- parasympathetic, sympathetic sensory vasodilator nerves
- sympathetic vasoconstrictor nerves
- Adrenaline, Angiotensin II, Vasopressin, ANP
What are the roles of intrinsic and extrinsic control?
INTRINSIC CONTROL:
- regulates local blood flow to organs/tissues (regional hyperaemia)
EXTRINSIC CONTROL:
- regulates TPR to control blood pressure
- brain function selectivity alters blood flow to organs according to need
- NERVES (vasoconstrictors, eg. noradrenaline, and vasodilators, eg. acetylcholine and NO)
- HORMONES (vasoconstrictors, eg.adrenaline, angiotensin II, vasopressin, and vasodilators, eg. anti-natriuretic peptide (ANP) )
Describe the mechanism of the most widespread and important extrinsic control.
The most important and widespread extrinsic control is the sympathetic vasoconstrictor system.
The Rostral Ventral Lateral Medulla (RVLM) of the brain recieves information from the Caudal VentroLateral Medulla (CVLM).
It then sends a signal down the main excitatory drive to the thoracic (T1-L2) spinal cord. This goes through the intermediolateral cell collumn (IML) of the spinal neurones, which contain pre-ganglionic sympathetic neurones.
It then sends a signal down the sympathetic fibres to release noradrenaline for vasoconstriction. This increases the BP and SV in the heart. It also sends signals down to the adrenal medulla to release adrenaline, which causes α1 constriction (but β2 relaxation).
RECAP: describe how sympathetic innervation of the arterioles leads to release of NA, and what becomes of it.
1) An action potential moves down the axon and arrives at a varicosity. A varicosity innervates the adventitia, the outermost layer of a blood vessel wall.
2) Depolarisation occurs at the varicosity, activating voltage-gated Ca2+ channels.
3) An ingress of Ca2+ causes the release of neurotransmitters, mainly noradrenaline.
4) The noradrenaline diffuses to the vascular smooth muscle where it mainly binds to α1, causing constriction. It will also bind to some α2, causing constriction, and β2, causing relaxation. There is a modulation of responses in both constriction and dilation.
5) The noradrenaline is then taken up again, and either recycled or broken down.
Adrenaline from the adrenal glands that is released into the blood circulation can also act as α1 or β2 receptors.
Describe what happens at the varicosity in detail.
The release of NA can be modulated by Angiotensin II acting on the AT1 receptor, increasing NA release. It does this by increasing cAMP production, which increases the calcium influx via VGCC, which induce the release of NA.
Metabolites prevent vasoconstriction to maintain blood flow. K+, adenosine, histamine, serotonin, etc. work via negative feedback by inhibiting NA release (which they do by inhibiting cAMP production).
NA can also give negative feeback by binding to α2 receptors on the varicosity to limit its own release.
Lots of modulation occurs at the neurotransmitter level at the varicosity. It produces vasoconstriction and vasodilation as required.
What are some important points about sympathetic vasoconstrictor nerves?
- they are controlled by the brain stem (provides control of blood flow/ blood pressure)
- it innervates most of the arterioles and veins of the body
- sympathetic nerve activity is tonic; tonic sympathetic activity sets vascular tone
- a decrease in sympathetic activity producing vasodilation is an important principle in pharmacological treatment of cardiovascular disease
What are the main roles of the sympathetic vasoconstrictor nerves (with cardiovascular parameters)?
- CONTRACT RESISTANCE ARTERIOLES
produces a vascular tone which allows vasodilation/increased blood flow to occurs, which controls TPR. - DISTINCT RVLM NEURONES (sympathetic pathways innervate different tissues)
we can switch vasoconstriction on in some vessels and off in others - PRE-CAPILLARY VASOCONSTRICTION
this leads to a downstream capillary pressure drop, so there is an increased absorption of interstitial fluid into the blood plasma to maintain blood volume - CONTROLS TPR
it maintains arterial blood pressure and blood flow to the brain/myocardium area (since Pa = CO x TPR) - CONTROLS VENOUS BLOOD VOLUME
venoconstriction leads to a decreased venous blood volume, so increasing the venous return; this increases the stroke volume via Starling’s Law
Describe vasodilator nerves.
A few specialised tissues contain vasodilator nerves, as well as vasoconstrictor nerves.
Normally, they have a specific function controlling a specific vascular bed rather than global functions.
Vasodilation occurs as the vascular tone produced by sympathetic vasoconstrictor nerves is inhibited.
There are mainly parasympathetic vasodilator nerves, and a few sympathetic vasodilator nerves (nociceptive C fibres)
Where are parasympathetic and sympathetic vasodilator nerves found?
PARASYMPATHETIC:
- salivary glands (release Ach and VIP)
- pancreas and intestinal mucosa (release VIP)
- male genitalia (release NO)
SYMPATHETIC:
- skin (sudomotor fibres) (release Ach and VIP)
Describe the effect of stimulation of sensory (nociceptive C fibres) vasodilator fibres.
The stimulationof sensory axon reflex (C-fibres) occurs by trauma, infection, etc.
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 the histamine and CGRP produce vasodilation, seen as the ‘flare’ in the skin.
Name some hormones that affect the control of circulation.
VASOCONSTRICTORS:
- adrenaline
- angiotensin II
- vasopressin (anti-diuretic hormone, ADH)
VASODILATORS:
- atrial natriuretic peptide (ANP)
OTHERS:
- insulin
- oestrogen
- relaxin
Where do noradrenaline and adrenline work, and what is their effect?
In most tissues, such as the GI tract and skin, adrenaline and noradrenaline both cause vasoconstriction.
In skeletal muscle and coronary circulation, adrenaline causes vasodilation, while noradrenaline still causes vasoconstriction.
Adrenaline mainly acts at the β2 receptors to dilate the vessels.
Noradrenaline acts mainly on the α1 receptors to constrict vessels.
Describe the effects of iv adrenaline and iv noradrenaline on common cardiovascular parameters.
When given ADRENALINE,
- the heart rate increases.
- The cardiac output also increases, but because the total peripheral resistance decreases (due to its effects on the β2 receptors),
- there is not much of an effect on blood pressure.
When given NORADRENALINE,
- there is a big increase in TPR (due to vasoconstriction at the α1 receptors),
- which causes an increase in blood pressure.
- This increased BP stimulates the baroreceptors’ reflex to decrease heart rate.
Describe a situation in which the renin-angiotensin-aldosterone system (RAAS) responds to lowered BP.
When our blood pressure is lowered, this is sensed by the body, and the kidneys release Renin from the JGA (juxtaglomerular apparatus). This converts Angiotensinogen to Angiotensin I. An enzyme called ACE (angiotensin-converting enzyme) is released from the lungs, which converts Angiotensin I to Angiotensin II.
Angiotensin II leads to vasoconstriction, which increases blood pressure. It also works by inducing the release of Aldosterone (a steroid hormone) from the cortex of the adrenal gland. It is also a mineralocortecoid, meaning it influences the salt, and thus, the water balances in the body. It works on the kidneys to increase water retention by Na+ movement, thus increasing the blood volume, which increases the blood pressure.
Describe how vasopressin responds to lowered BP.
A hypothalamus response is stimulated by an increase in osmolarity (ie. dehydration, lowered BP).
The hypothalamus then forms Vasopressin or ADH, which is then transported via axons to the posterior pituitary, which releases it into the blood.
Vasopressin causes vasoconstriction, along with increased renal absorption of water. Both of these effects help maintain the blood pressure.
Stretch receptors in the left atrium send continuous signals, causing firing in the NTS (nucleus tractus solitarius). This sends out inhibitory signals to the CVLM. The CVLM (caudal ventrolateral medulla) stimulates the pituitary to release vasopressin, so the stretching of the heart inhibits this.
With a dehydration or a haemorrhage, the NTS’s inhibition is switched off and the CVLM stimulates vasopressin production. The NTS is like the thermostat that sets the level at which the CVLM is inhibited.
