endothelium Flashcards
vasodilator nerves
how does vasoldilation occur?
name the 3 nerves that allow this to happen
A few specialised tissues contain vasodilator nerves,
as well as vasoconstrictor nerves
Normally have an specific function
Vasodilatation occurs as vascular tone
produced by sympathetic vasoconstrictor nerves is inhibited by:
Parasympathetic vasodilator nerves
Sympathetic vasodilator nerves
Sensory (nociceptive C fibres) vasodilator nerves
Parasympathetic Vasodilator Nerves - where and what do they release
what is unique to these tissues?
where do the neurotransmitters act on? effect?
Salivary glands – release Ach / VIP
Pancreas & intestinal mucosa – release VIP
Both these tissues need high blood flow to maintain
Parasympathetic-mediated fluid secretion
So, parasympathetic nerves release Ach/VIP act on endothelium to cause release of NO – vasodilatation in these tissues
Parasympathetic Vasodilator Nerves - erectile tissue
what is released by the nerve? what does this produce and lead to?
name the drug that enhance this effect
how does it enhance the effect?
Release of NO by parasympathetic nerves causes production of cGMP which leads to vasodilatation
Sildenafil (Viagra) enhances this effect of NO by blocking the breakdown of cGMP by phosophodiesterase 5
Sympathetic Vasodilator Nerves - where and what do they release
where do they act? what else are these fibres called? what is released?
what is the vasodilation associated with in this area?
explain why
what will sympathetic consctriction do in this area?
explain blushing
Skin (sudomotor fibres) – release Ach, VIP
Vasodilatation associated with sympathetic-mediated sweating
Makes sense, e.g. Hot weather, exercise
Need more blood flow, to make more sweat,
Need more blood flow to skin
Both help to cool down
Sympathetic vasoconstriction would only reduce blood flow
limit sweat production, limit cooling down
Head, face, upper chest, involved in blushing
Stress (sympathetic) response – do you know anyone that suffers!
Sensory (nociceptive C fibres) vasodilator fibres
where does info go when c fibres are stimulated? (2)
what is released in one of these routes? what do they act on? (2) what do these both release?
examples of what can stimulate them
Stimulation of sensory axon reflex (C-fibres) by trauma, infection etc
will send info to spinal chord (go up to brain)
Also, send info via axon collateral to Release Sub P, CGRP
1) Act on Mast cells to release histamine
2) Act on endothelium and VSM
Both produce vasodilatation called ‘’Flare’’ in skin
what causes Endothelium-derived relaxing factors(EDRF) - Nitric oxide (NO) to be produced?
2 main groups
examples of molecules from one of these groups
importance of this
Shear stress from blood flow, Inflammatory factors (Sub P, histamine, bradykinin, Ach)
hence blood flow causes constant production of NO therefore vasodilitation
How does blood flow through shear stress help regulate vascular tone?
signficance of shear stress and importance of this?
Blood flow (through shear stress) -> Constant release of NO Vascular tone control by Tonic sympathetic activity (constriction) + Tonic NO release (dilation) hence a shift can lead to constriction or dilitation
How do EDRF release NO?
what will shear stress lead to? what do this act on to produce NO?
Shear stress/factors in the endothelium will act on receptor which will activate the (endothelium nitric oxide synthase) eNOS enzyme which produce NO from the amino acid arginine
How does NO cause vasodilation?
what is important about NO?
where does it go and what does it stimulate? what does this do and effect of this?
NO is a gas and lipophillic so it moves out of the eptihelium and moves to the adjacent muscle cells where it stimulates the GC enzyme (Guanylate cyclase) which converts it from GMP -> cGMP -> PKG which causes vasodilation
Importance of the EDRF, Prostacyclin (PGI2)
what is the importance of PGI2? (2)
what reduces PGI2? clincial importance of this?
where else is this used in the body?
Tonic PGI2 production important in maintaining blood flow in renal arterioles
Needed to maintain glomerular filtration rate (GFR),
and kidney function
- COX inhibition (NSAIDs), reducing PGI2, is potentially dangerous in kidney failure -
Also, important pathway in inflammation-mediated vasodilation
PGI2 pathway
what will act on receptors? what does this cause to become PGI2? via what?
where will the PGI2 act and what does this activate? what does this lead to?
e.g. Shear stress, Inflammatory factors, Ach will act on receptors which causes membrane lipids to become PGI2 due to cyclooxygenase (COX)
The PGI2 will act on the prostanoid receptor (PGI2) which activates the Gs pathways therefore adenyl cyclase will cause ATP to turn into more cAMP and activate the PKA pathway eventually leadign to vasodilation
Why do PKA and PKG produce vasodilatation?
what is the pkg pathway? and the PKA pathway?
what are the 3 actions in VSMC?
what is the net effect of these 3 actions?
GC – cGMP - PKG pathway
Gs – cAMP – PKA pathway
Vasodilation
Action of PKG and PKA in vascular smooth muscle cells
(1) Increased Ca ATPase (SERCA) – increase uptake into SR and exclusion from cell
(2) Increased K channel activity -> hyperpolarisation -> decreased VGCCs
(3) Decreased MLCK
All these actions in reduce Ca2+ levels
and reduce action of contractile mechanisms
Endothelium-derived hyperpolarisation factor - K+
what will act on receptors?
what does this lead to the activation of?
what is the significance of the location?
where will this molecule act on and what effect will it have? (2)
net effect of this?
e.g. Shear stress from blood flow, Inflammatory factors (Sub P, histamine, bradykinin, Ach)
Will act on receptor leading to the activation of K+ channels leads to a rise in local external K+ levels between muscle cells and epithelium
This acts on vascular smooth muscle cells which switches on K+ channels and increases Na/K ATPase hence 3Na+ out and 2K+ in
Both lead to hyperpolarisation of VSMCs
Decrease VGCCs and Ca entry
Vasodilation
Endothelium-derived hyperpolarisation (EDH)
what will act on receptors?
what does this lead to the activation of?
what is here that is significant?
net effect?
e.g. Shear stress from blood flow, Inflammatory factors (Sub P, histamine, BK), Ach
Will act on receptor leading to the activation of K+ channels leading to hyperpolarisation which will be pumped out BUT there are connections between endothelium and smooth muscle cells too
GAP junctions between endothelium and VSMCS
Conduction of hyperpolarisation from endothelium to VSMCs
Decrease VGCCs and Ca entry -> Vasodilation
How does b2 adrenoceptors on vsmcs produce vasodilation?
what does stimulation of B2 adrenorecptors cause?
what activity does it lead to?
what effects does it have?
what is it important for? (2)
stimulation of B2-adrenoceptors on VSMCs
produces vasodilatation in coronary and skeletal muscle arterioles
B2-adrenoceptor stimulation -> PKA activity
(1) Increased Ca ATPase (SERCA) – increase uptake into SR/exclusion from cell
(2) Increased K channel activity -> hyperpolarisation -> Decreased VGCCs
(3) Decreased MLCK
Important for increasing blood flow to heart and skeletal muscle during exercise
