Lecture 6 - Intrinsic and Extrinsic control of circulation Flashcards
What allows arterioels to vasoconstrict and dilate to control resistance?
And, what does the aorta and large arteries act as in the CVS?
Conversely, what do small arteries and aerterioles act as in the CVS?
The smooth muscle allows for this.
The aorta and large arteries are the high pressure conduits that provide the pressure head that drives blood through the systemic circuit.
Whereas smaller arteries and arterioles act as the resistance vessels. It’s the control of these vessels that determines volume flow through the circulation.
What is vascular tone?
This is the tension exerted by vascular smooth muscle cells. Vascular tone regulates the radius (calibre) of the resistance vessels, and hence blood flow through it.
An increase in tone causes vasoconstriction, leading to reduced local blood flow.
Whereas a decrease in tone causes vasodilation, which causes decreased local blood flow.
What variable does vascular tone regulate?
Vascular tone regulates arterial blood pressure.
MABP = CO x TPR
- There is continuous adjustment of resistance vessel tone that helps to control blood pressure during:
- Standing up
- Hypovolemic emergencies - haemorrhage
Vascular tone is controlled by intrinsic and extrinsic mechanisms.
What are the intrinsic mechanisms?
- Myogeneic response
- Paracrine factors (metabolites, NO)
- Physical factors (temperature, pressure)
They are local factors because they have no CNS input. If local factors can’t maintain adequate perfusion then the central system comes into play.
What are the extrinsic mechansism that control vascular tone?
- Vasodilator nerves
- Sympathetic vasoconstrictor nerves
- Endocrine factors (adrenaline, angiotensin, vasopressin, etc.)
In intrinsic control via instrinic mechanisms of vascular tone, when arterial pressure is altered blood flow in many vascular beds stays constant, this is called what?
Describe what occurs
Autoregulation.
This autoregulation is done via the myogenic response, the resistance vessels respond directly to a change in pressure by vasonconstriction of vasodilation.
e.g. If there is decrease arterial pressure, there is decreased blood flow to an organ. Skeletal muscle uses O2 (potetent vasoconstrictor) and releases CO2 (vasodilator). So if there is decreased blood flow, less O2 is being supplied and less CO2 is being removed - the net result is vasodilation. The vasodilation increases blood flow, which results in increased O2 supply and CO2 removal, which can constricts the vessel. There is a balance between the vasodilation and constriction to maintain the correct blood pressure. (L-type Ca2+ channels play an improtant role in the myogeneic response).
When the vessels narrow due to the myogenic response, there is increased endothelial shear stress which resultsin in endothelium producing NO -> this prevents excessive myogenic constriction.
If the blood pressure changes between ~40-60mmHg, it will be held constant by the myogenic response in intrinsic regulation.
Describe metabolic regulation (active hyperemia)
Metabolic regulation operates by releasing local dilator substances (CO2, lactic acid, hydrogen ions, etc.)
This helps to maintain the blood flow to organs like the brain, heart muscle and skeletal muscle to match metabolic activity.
As the rate of metabolism increases, blood flow increases due to vasodilation. And as blood flow increases, aterial O2 saturation increases.
What is reactive hypermia?
This is vasodilation of vessels downstream from an occlusion (complete obstruction to blood flow)
The downstream arterioles continue to metabolise despite having no blood flow. They use up the O2 and produce CO2, this causes them to dilate. This is beneficial, because when the occlusion is removed the downstream arterioles have increased blood flow.
This occurs in conditions like myocardial infarction, peripheral artery disease.
How is tissue blood flow controled endothelial derived factors?
Endothelium produces both vasoconstrictors and vasodialtors.
Vasoconstrictors
- Endothelin
- Angiotensin II
Vasodilators
- NO
- Prostacyclin (PGI2)
- Endothelial derived hyperpolarizing factor (EDHF)
- Adenosine (potent vasodilator in heart
How does NO control vascular tone, and where is it derived from?
60-80% of NO production from endothelium comes from shear stress. Circulating insulin and oestrogen can activate NO production to a lesser extenet.
As the radius or arteriole constricts, this increases shear stress and this increases NO release.
IT IS SHEAR STRESS, NO FLOW, THAT INCREASES NO PRODUCTION
Shear stress activates the PKB pathway. NO goes into smooth muscle cells, which enter cGTP pathway to cause relaxation.
- only has a half life of 6 seconds
Maintenece of a balance between tonic relaxation induced by NO and tonic vasoconstriction from the myogenic response is necessary to maintain normal blood flow.
What factors affect NO production?
- Shear stress - increased in atherosclerosis and exercise(increased velocity of blood)
- Pregnancy
- Due to high oestrogen levels, which causes generalized vasodilation.
- Despite a 50% increase in CO, TPR falls, hence MAP decreases.
- Drugs
- GTN, sodium nitroprusside & isosorbide dinitrate.
- used as vasodilators to treate cardiac angina
- act by mimicking endothelial NO
- Effective venodilators and large artery dilators
- The therapeutic benefit is due to
- Reduction of central venous pressure
- reduction of systolic blood pressure
What makes up the control hierarchy of vascular tone?
What is the purpose of having extrinsic controls of blood vessels?
And what are they?
To regulate overall TPR to control blood pressure, and to allow the brain to alter blood flow selectively to individual organs when theres a change in conditions (e.g. vasodilation of secreting salivary gland)
- Vasomotor nerves (vasoconstrictor, vasodilator)
- Hormones (Adrenaline, vasopressin, angiotensin II)
Symathetic vasoconstrictor fibres (noradrenergic) are that most widespread and important for extrinsic control.
Descirbe the innervation of blood vessels via the SNS
Bulbospinal fibres synapase with sympathetic pre-gang fibres, which run down and synapse with a post- gang sympathetic fire to activate the alpha adrenoreceptors.
Describe how the sympathetic vasoconstrictor nerves are controlled, what they innervatem and how they terminate.
Vasoconstrictor nerves are controlled by the brainstem (by vasomotor centre), and innervate most arterioles & veins of the body.
They terminate at the edge of the tunica media, in strings of synaptic varicosities. These varicosities release dense cored vesicles containing noradrenaline and ATP onto and activate alpha adrenergic receptors on vascular myocytes.
Alpha-adrenoreceptors always cause vasoconstriction.
What happens to vascular tone with increased sympathetic activity?
Increased sympathetic activity leads to vasoconstriction.
Where are vasodilator nerves found, what function do they have?
They are found in organs where the brain needs to control and command a profound increase in blood flow.
AcH and vasoactive intestinal peptide (VIP) are comon transmitters released by PNS fibres.
What hormones control circulation
How does adrenaline work
It’s a hormone released by the adrenal medulla - it is the main catecholamine secreted by the human adrenal medulla .
Plasma epinephrine from the adrenal medulla acts on alpha and B2 receptors (since there are way more alpha receptors epinephrine causes vasoconstriction, no dilation)
What are the hormonal factors controlling circulation?
Overall summary
