L10: Autonomic control of CVS Flashcards
What is the ANS important for?
Regulating physiological functions
HR, BP, Body temperature, coordinating body’s response to exercise and stress
Control over–> smooth muscle, exocrine secretion and rate and force of contraction of the heart
Maintain balance
What are the divisions of the ANS?
Sympathetic--> fight or flight --> thoracolumbar outflow --> tissue can be independently regulated or it can be a more generalised Parasympathetic--> rest or digest --> craniosacral outflow
What is the arrangement of the pre- and post ganglionic fibres in the sympathetic and parasympathetic system?
Sympathetic --> Short pre --> Long post --> ganglia in sympathetic chain Para- --> Long pre --> Short post --> Ganglia in or close to target organ
What affect does the sympathetic and parasympathetic nervous system have on the pupil of the eye? What are the main receptors involved?
Sympathetic–> Dilation –> constriction of radial eye muscles–> need to be able to see danger
–> α1
Parasympathetic –> Constriction–> contracts sphincter muscles
–> Muscarinic - M3
What affect does the sympathetic and parasympathetic nervous system have on the lung? What are the main receptors involved?
Sympathetic–> bronchiodilation
–> β2
Parasympathetic–> bronchochonstriction
–> M3
What affect does the sympathetic and parasympathetic nervous system have on the heart? What are the main receptors involved?
Sympathetic–> ↑HR and force of contraction (+ve Chrontrophy)
–> β1
Parasympathetic–> ↓ HR
–> M2
What affect does the sympathetic and parasympathetic nervous system have on the sweat glands? What are the main receptors involved?
Sympathetic–> increase sweat production –> keep cool
–> localised secretion–> α1
–> generalised secretion –> M3
Parasympathetic–> no effect
What role does the ANS play in the cardiovascular system?
Control HR, force of contraction and peripheral resistance of vasculature
What happens if you de-innervate the heart?
Heart will still beat
ANS does not initate the electrical activity
Beats at faster rate–> normally under control of vagus nerve
What is the parasympathetic input to the heart?
Via vagus (X) nerve–> synapse on postganglionic cells in the SA and AV node–> Post- ACh onto receptors
M2 receptors
–> Decrease HR
–> Decrease AV node conduction velocity
What is the sympathetic input to the heart?
Preganglionic–> sympathetic chain–> Post- NA onto receptors
Innervate SA, AV node and myocardium
β1 receptors
–> Increase HR
–> Increase force of contraction (+ve chronotrophic effect)
What do we mean by the pacemaker of the heart?
The Sinoatrial node controls the heart rate–> rhythm
How does the pacemaker of the heart work?
Slow depolarising pacemaker potential–> funny current (If)–> slow inward current of Na+ ions (HCN channels)
Hits threshold–> fast Ca2+ channels open–> Ca2+ influx
Peak
Closing of Ca2+ channels opening of K+ channels–> repolarisation
What are HCN channels?
Hyperpolarisation-activated Cyclic Nucleotide gated channels
How does the sympathetic system effect the pacemaker potential of the heart?
Speeds up pacemaker potential
Increases the slope to threshold
Mediated by NA on β1 receptors–> ↑cAMP (acts on HCN channels)
How does the parasympathetic system effect the pacemaker potential?
Slows down the pacemaker potential
Decrease the slope
Vagal nerve
Mediated by ACh on M2 receptors–>GPCR–> Gi –> ↑K+ conductance and decrease cAMP (reduced HCN activity)
How does NA increase the force of contraction of heart?
β1 receptors--> GPCR ↑ cAMP--> ↑ PKA -Phosphorylation of Ca2+ channels--> ↑Ca2+ entry during plateau phase of cardiomyocyte AP--> prolonges depolarisation -Increase Ca2+ uptake in SR Increase force of contraction
How does the ANS affect the vasculature?
Mostly sympathetic innervation (some exceptions -erectile tissue)
α1 receptors
Coronary, liver and Skeletal Muscle vasculature also have β2 receptors
How is vasculature regulated?
Vasomotor tone–> normal basal level
↑NA acts on α1 receptors–> vasoconstriction
↓NA less activation of α1 receptors–> vasodilation
What is the effect of having α1 and β2 receptors in vasculature?
NA controls muscle vasculature without fight or flight (sympathetic input)
Adrenaline released from adrenal glands
–> Low levels (physiological concn) acts on β2 receptors–> vasodilation
–> higher binding affinity
–> High levels also acts on α1 receptors–> vasoconstriction (fight or flight ↑ adrenaline= vasoconstriction)
(b2 on skeletal muscle, myocardium and liver)
What is the specific mechanism behind effect of B2 and a1 receptors in vascular smooth muscle?
- Adrenaline–> β2 –> αs subunit–> AC–> ↑cAMP–> PKA–> Open K+ channels and inhibit MLCK–> Vasodilation
- Adrenaline–> α1 –> αq subunit–> PC–> PIP2–> IP3 and DAG–> IP3 ↑Ca2+–> activates MLCK–> phosphorylates myosin light chain = activation (contraction)–> Also DAG –> PKC–> inhibit MLCP –> Vasoconstriction
What is the most important thing for dilating blood vessels?
Local metabolites produced by active tissue (adenosine, potassium, H+ (pH change), CO2)
More important for ensureing adequate perfusion of skeletal and coronary muscle than activation of β2 receptors
How does the brain know whether to vasoconstrict or vasodilate blood vessels?
Baroreceptors –> arch of aorta and carotid sinus–> high pressure system
Atrial receptors –> low pressure system
How do the baroreceptors detect changes in blood pressure?
Stretch receptors
Increase pressure–> stretches baroreceptors (glossopharyngeal in CS, vagus in AA) –> Increase AP firing to brain
Decreases pressure–> less stretch –> decrease AP firing to brain
What is the pathway for changing blood pressure?
↑ arterial blood pressure –> Baroreceptors detect stretch–> ↑ AP to medulla –> Efferent pathway –> ↓ HR, CO and vasodilate vessels –> ↓ arterial pressure
↓ arterial blood pressure –> Baroreceptors detect decreased stretch–> ↓ AP to medulla –> Efferent pathway –> ↑ HR, CO and vasoconstriction of vessels –> ↓ arterial pressure
Check lecture note slide 26
What is the problem with prolonged high blood pressure?
Baroreceptors re-set to higher level
Elevated BP no longer stretched baroreceptors so no AP fired
What drugs can act on the ANS?
Sympathomimetics–> Adrenoreceptor agonists
Adrenoreceptor antagonists
Cholinergics–> Muscarinic agonists and antagonists
What are the uses of sympathomimetics?
Mimic agonists
α1–> pharmacological dose of adrenaline
–> cardiac arrest–> Vasoconstriction of BV increase blood flow to heart
–> Anaphylactic shock–> Overcome effects of β2 receptors (vasculature) activating α1 –> vasoconstriction
β1–> Dobutamine–> cardiogenic shock (heart can’t pump enough blood to meet needs)–> increases force of contraction in the heart and heart rate (without tachycardia)
β2–> Salbutamol–> Asthma–> Receptors in the lung causes bronchodilation
What is the use of adrenoreceptor antagonists?
Prazosin–> a1 adrenoreceptor antagonist–> vasodilation of vasculature
Propanolol–> b1/b2 non selective antagonist
- b1–> decrease heart rate, reduce force of contraction
- b2–> bronchoconstriction
Atenolol–> B1 selective
-decrease HR and force of contraction without affecting lungs
CONFUSING EXPLAINATION
α adrenoreceptor antagonists–> inhibit NA on α1–> vasodilation e.g. prazosin antihypertensive drug
β adrenoreceptor antagonists–>
- -> Propranolol–> non selective β1/β2 antagonist–> β1 slows heart rate, β2 bronchoconstriction
- -> atenolol–> selective β1 (cardio-selective)–> slows HR less risk of bronchoconstriction
What is the use of cholinergics?
Muscarinic agonist –>
–> Pilocarpine –> treatment of gluacoma–> activates constrictor pupillae muscles (M3)
Muscarinic antagonists
–> Atropine and tropicamide
–> increase HR and bronchial dilation (M2 + M3)
–> used to dilate pupils for the eye (M3)
