The Sympathetic Nervous System Flashcards
What are the physiological effects on the heart (SNS)?
Noradrenaline increase:
Force of contraction (positive inotropy)
Rate of contraction (positive chronotropy)
Rate of relaxation (positive lusitropy)
What effects does it cause on different blood vessels and other smooth muscle ?
(SNS)
NA or adrenaline produce smooth muscle contraction causing artery narrowing
Certain arteries like coronary and skeletal muscle relax to adrenaline
Bladder, uterus and GI smooth muscle relax to sympathetic nerve activation
Airway smooth muscle relaxes to adrenergics
SNS effects on kidney?
Juxta glomerular apparatus(JGA)
Located between afferent and efferent renal arteries
Has a rich innovation in sympathetic nerves
When you stimulate sympathetic nerves going to the kidney it will increase renin release
Renin converts an agent called angiotensinogen found in our blood to angiotensin I
Angiotensinogen(Inactive) ——> Angiotensin I (active)
Angiotensin I has some biological effect but it is further converted by an enzyme into angiotensin II which is a very potent vasoconstrictor.
It also increases circulating blood volume and has effects on cardiac remodelling.
SNS effects on liver and skeletal muscle?
Sympathetic nerve activation affects not the cells themselves but the energy stores within it ( key targets are circled in red)
Increased nerve activation by turning on a phosphorylase both in the muscle and the liver you get increased glycogenolysis
Increased lipolysis by stimulating the lipase in fat
Which means increased glucose and TCA cycle intermediates
SNS effects on eyes?
The sympathetic nerve innervates the radial muscle in our eye and stimulating it leads to contraction which leads to a wider pupil
The production of aqueous humour is controlled to SOME extent by the sympathetic nervous system (it increases production)
SNS effects on sweat and hair?
Our hairs have little piloerector muscles attached to the base
Sympathetic nerve causes piloerection- the muscle contracts which pulls on the base of the hair to make the hairs stand on end
Increases sweat production (NOT mediated by noradrenaline but rather acetylcholine)
What are the different types of adrenergic receptors and their potency?
Remember this receptor has 7 transmembrane domains
“>” means more potent
alpha where noradrenaline > adrenaline > isoprenaline (a synthetic compound NOT in our bodies
beta where isoprenaline > adrenaline > noradrenaline
Development of selective antagonists and molecular biological techniques
What effect do each of the different classes of adrenoceptors cause?
Alpha 1 - vascular smooth muscle contraction
Alpha 2- inhibition of transmitter release on the sympathetic nerve terminals
Beta 1- main cardiac effects( stimulatory effect on the heart)
Beta 2-vascular dilation/ airway relaxation
Beta 2 and 3- adrenoreceptor activation are also involved in the metabolic effects
How do alpha 1 adrenoceptors achieve smooth muscle contraction?
The receptor is coupled to an alpha GQ/G11 and the blue thing next to it is phospholipase C which interacts with PIP2 which gets cleaved to leave diacylglycerol (DAG) and IP3
IP3 binds to its own receptor and releases calcium ions from internal stores
How do alpha 2 adrenoceptors work?
Alpha 2 adrenoceptors are negatively linked to adenylate cyclase therefore decreased cAMP and as a consequence the activation of these calcium ion channels occurs less often so even with an action potential the ion channels are less responsive meaning decreased vesicular fusion
How do beta 1 adrenoceptors achieve cardiac contraction?
So we have beta1 adrenoceptors predominantly expressed in the heart which are coupled to adenylate cyclase which makes cyclic AMP
Cyclic AMP binds directly to a channel in the pacemaker region of the heart called the sinoatrial node or the atrial ventricular nodes and, by binding, it makes these channels more active meaning these regions depolarise quicker.
cAMP also tends to interact via mediators, and the main one is protein kinase A (PKA).
cAMP sticks a phosphate group on a protein which alters how the protein operates, in this case, PKA turns on calcium channels.
All that calcium coming in leads to more forceful contraction
PKA also activates potassium channels which explains the more brief nature of the cardic action potential
PKA work on the calcium release channels but also on the calcium uptake channels meaning the cardiac myocytes can relax quicker
How do beta1/2 adrenoceptors achieve relaxation of smooth muscle?
Especially airways
Skeletal muscle vasculature
Also coronary and cerebral blood vessels
This effect has nothing to do with the receptor but rather with the way the muscles contract
In cardiac myosin it is the removal of tropomyosin that allows the two proteins to come together
In smooth muscle the increase in calcium leads to the activation of a ‘go’ mechanism called Myosin Light chain kinase that stimulates the smooth muscle myosin
This Myosin Light chain kinase is inhibited by protein kinase A
What are beta adrenoceptors also linked to?
Carbohydrate metabolism(beta1)
Lipolysis(beta3) this is through manipulating enzymes as the lipase is sensitive to PKA action
Influence renin release from kidney(beta3)
