Nervous and hormonal control of vascular tone Flashcards
What is intrinsic control?
→ Regulates local blood flow to organs/ tissues
→ Important - regional hyperaemia (increase in blood flow)
What is extrinsic control?
→ Regulates TPR to control blood pressure
→ Brain function selectivity alters blood flow to organs according to need
What are vasoconstrictor hormones?
→ Adrenaline, angiotensin II, vasopressin
What is a vasodilator hormone?
→ Atrial Natriuretic Peptide
What is the most widespread and important form of extrinsic control?
→Sympathetic vasoconstriction
→ Nervous system information integrated by the brain
How does sympathetic innervation of the arterioles leads to release of NA?
1) Action potential moves down the axon and arrives at a varicosity
2) Depolarization at the varicosity activates voltage gates Ca2+ channels
3) Ingress of Ca2+ causes the release of neurotransmitters - mainly NA
4) NA diffuses into the vascular smooth muscle cells
What are the three receptors NA binds to and what are the effects?
→ alpha 1 - contraction
→ alpha 2 - contraction
→ beta 2 - relaxation
How can the release of NA be modulated?
→ by Angiotensin II acting on AT 1 receptor which increases NA release
→metabolites prevent vasoconstriction and maintain blood flow
→K+, adenosine, histamine & serotonin feedback and inhibit NA release
→ NA can also negatively feed back itself via a2 receptors to limit its own release.
what does lots of modulation occurring at the NT level produce?
→ Produces vasoconstriction + vasodilation as required
What are sympathetic vasoconstrictor nerves controlled by?
→ controlled by the brain stem (provides control of blood flow/ blood pressure)
What do sympathetic vasoconstrictor nerves innervate?
→innervates most of the arterioles and veins of the body
What kind of activity do sympathetic nerves have?
→sympathetic nerve activity is tonic
→ tonic sympathetic activity sets vascular tone
What is an important principle in pharmacological treatment of CVS diseases with regards to sympathetic activity?
→a decrease in sympathetic activity producing vasodilation is an important principle in pharmacological treatment of cardiovascular disease
How do sympathetic vasoconstrictor nerves contract resistance arterioles?
Produce vascular tone which allows vasodilation/increased blood flow to occur which controls TPR
What do DISTINCT RVLM NEURONES do?
(sympathetic pathways innervate different tissues)
we can switch vasoconstriction on in some vessels and off in others
What does pre-capillary vasoconstriction do?
→this leads to a downstream capillary pressure drop
→ increased absorption of interstitial fluid into the blood plasma to maintain blood volume
How do sympathetic vasoconstrictor nerves control TPR?
→it maintains arterial blood pressure and blood flow to the brain/myocardium area (since Pa = CO x TPR)
What does venoconstriction lead to?
→ venoconstriction leads to a decreased venous blood volume
→ increasing the venous return
→ increases the stroke volume via Starling’s Law
What types of tissues contain vasodilator nerves and what is their function?
→ A few specialised tissues contain vasodilator nerves, as well as vasoconstrictor nerves.
→ they have a specific function controlling a specific vascular bed rather than global functions.
How does vasodilation occur?
Vasodilation occurs as the vascular tone produced by sympathetic vasoconstrictor nerves is inhibited.
What are the innervations of vasodilator nerves?
There are mainly parasympathetic vasodilator nerves, and a few sympathetic vasodilator nerves
Where are parasympathetic vasodilator nerves found?
→salivary glands (release Ach and VIP)
→ pancreas and intestinal mucosa (release VIP)
→ male genitalia (release NO)
Where are sympathetic vasodilator nerves found?
→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.
What is the Lewis triple response?
→ Local redness
→ Wheal
→ Flare
What are 3 vasoconstrictor hormones?
→ Adrenaline
→Angiotensin II
→ Vasopressin (ADH)
What are 3 hormones that affect the circulation?
→ estrogen, insulin, relaxin
Where is adrenaline released from?
→ Adrenal medulla via the action of AcH on nicotinic receptors
When is adrenaline released?
→ Exercise
→ fight or flight
→ Hypotension
→ Hypoglycaemia
What are the main roles of adrenaline?
→ Glucose mobilization (skeletal muscle, glycogenolysis, fat lipolysis)
→ Stimulation of the heart rate and contractility during normal exercise
→ Vasodilation of coronary and skeletal muscle arteries
Why is there vasoconstriction in most tissue?
→ due to alpha 1 adrenoceptors
What receptors do skeletal muscles and coronary arteries have more of?
→ more beta 2 than alpha 1 adrenoceptors
What receptor does adrenaline have a higher affinity for?
→ Higher affinity for beta over alpha
What receptor does noradrenaline have a higher affinity for?
→ Higher affinity for alpha
Describe the effects of iv adrenaline on the heart
→ the heart rate increases.
→The cardiac output also increases
→ total peripheral resistance decreases (due to its effects on the β2 receptors)
→ not much of an effect on blood pressure.
Describe the effects of iv noradrenaline on the heart
→ big increase in TPR (due to vasoconstriction at the α1 receptors)
→ causes an increase in blood pressure.
→ increased BP stimulates the baroreceptors’ reflex to decrease heart rate.
How does the RAAS system work?
1) Renin is produced by the kidney, stimulated by low renal blood flow
2) Angiotensinogen is the precursor produced in the liver
3) undergoes proteolysis and becomes Angiotensin I which goes to the lungs
4) Angiotensin converting enzyme converts it into Angiotensin II (increased sympathetic drive, thirst)
5) Aldosterone is produced causes renal NaCl + H2O retention - raises blood volume
What is the hypothalamus response stimulated by?
→ An increase in osmolarity (dehydration or low blood volume)
Where is vasopressin or ADH released from?
→ Posterior of the pituitary gland
What does vasopressin or ADH release cause?
→ Vasoconstriction and increases renal absorption of water
→ maintains blood pressure
how does vasopressin respond to lowered BP?
→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 ADH
→ stretching of the heart inhibits release of ADH
What happens to the NTs during dehydration or haemorrhage?
→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.
What is ANP released by?
→ Specialised atrial myocytes
how is ANP is secreted?
→ Secreted by increased filling pressures which stimulate stretch receptors
Where does ANP act?
→ Acts at NP receptors on vascular smooth muscle cells
→Increases the cGMP pathway (like NO)
What does ANP do?
→ Systemic vasodilation
→Opposes the action of RAAS, ADH and noradrenaline
What does the dilation of the renal afferent arteriole do?
→ Increases GFR
→ Na+ and H2O excretion by the kidney are increased
→ blood volume goes down decreasing the release and/or actions of aldosterone, renin + ADH
