10. Autonomic Control Of CVS Flashcards
What is the autonomic nervous system important for regulating?
Heart rate, BP, body temp
Coordinating the body’s response to exercise and stress
Exerts control of smooth muscle, exocrine secretion and rate and force of contraction in heart
What are the functions of the autonomic nervous system?
Regulates physiological functions
Where parasympathetic and sympathetic divisions both innervate a tissue they often have opposite effects
Sympathetic activity increased under stress
Parasympathetic system more dominant under basal conditions
What are the sympathetic and parasympathetic effects on the pupil of the eye and what receptors are responsible?
Sympathetic - dilation (alpha 1)
Parasympathetic - contraction (M3)
What are the sympathetic and parasympathetic effects on the airways of the lungs and what receptors are responsible?
Sympathetic - relax (beta 2)
Parasympathetic - contract (M3)
What are the sympathetic and parasympathetic effects on the heart and what receptors are responsible?
Sympathetic - increase rate and force of contraction (beta 1)
Parasympathetic - decrease rate (M3)
What are the sympathetic and parasympathetic effects on the sweat glands and what receptors are responsible?
Sympathetic - localised secretion (alpha 1), generalised secretion (M3)
Parasympathetic - no effect
Give examples of when sympathetic drive to different tissues is independently regulated
Sympathetic activity to heart can be increased without increasing activity to GI tract
On some occasions (fight or flight) there can be a more coordinated sympathetic response
What does heart rate change when dennervated?
Increases, at a faster rate
Describe the parasympathetic input to the heart
Preganglionic fibres - 10th (X) cranial nerve - vagus
Synapse with postganglionic cells on epicardial surface or within walls of heart at SA and AV node
Postganglionic cells release ACh
Acts on M2 receptors to decrease heart rate and decrease AV node conduction velocity
Why can only the sympathetic input change the force of contraction?
Parasympathetic only innervates cells on epicardial surface or at SA and AV nodes
Sympathetic innervate at the SA and AV nodes and also in the myocardium, allowing it to change force of contraction
What is positive and negative chronotropism?
Positive - increases heart rate
Negative - decreases heart rate
Describe the sympathetic input to the heart
Postganglionic fibres from the sympathetic trunk
Innervate SA node, AV node and myocardium - release noradrenaline
Acts mainly on beta 1 adrenoceptors - increases heart rate, and increases force of contraction
What is the pacemaker of the heart?
Cells in the SA node steadily depolarise toward threshold:
- Slow depolarising pacemaker potential
- Turning on of a slow Na+ conductance (If - funny current)
- opening of Ca2+ channels
AP firing in SA node sets rhythm of heart
Describe the action potentials in SA node cells
Slow depolarising pacemaker potential If funny current (HCN channels)
Opening of fast Ca2+ channels - sharp upstroke
Closing of Ca2+ channels and opening of K+ channels - rapid repolarisation
Describe the effect of sympathetic activity on pacemaker potentials
Increases slope so reaches threshold quicker
Sympathetic effect mediated by beta 1 receptors
G-protein coupled receptors (Gs), increased cAMP, speeds up pacemaker potential
Increased cAMP increases opening of HCN channels so quicker to reach threshold
Describe the effect of parasympathetic activity on pacemaker potential
Decreases slope, reaches threshold slower
Parasympathetic effect mediated by M2 receptors
G-protein coupled receptors (Gi), increase K+ conductance and decrease cAMP
How does noradrenaline increase force of contraction?
NA acting on beta 1 receptors in myocardium causes an increase in cAMP and therefore activates PKA
1. Phosphorylation of Ca2+ channels increases Ca2+ entry during plateau of AP
2. Increased uptake of Ca2+ in sarcoplasmic reticulum
Lead to increased force of contraction
Describe the innervation of vasculature
Most vessels receive sympathetic innervation - except some specialised tissue have parasympathetic innervation e.g. erectile tissue
Most arteries and vins have alpha 1 adrenoceptors
Coronary and skeletal muscle vasculature also have B2 receptors
What does vasomotor tone allow for?
Vasodilation to occur
What happens with increased or decreased sympathetic output?
Increased = more noradrenaline, vasoconstriction Decreased = less noradrenaline, vasodilation
Which blood vessels have beta 1 and 2 adrenoceptors?
Skeletal muscle
Myocardium
Liver
What receptors does circulating adrenaline affect?
Beta 2 receptors, causing vasodilation
What happens when circulating adrenaline increases?
Circulating adrenaline has higher affinity for beta 2 adrenoceptors than for alpha 1 receptors
At physiological concentration circulating adrenaline will preferentially bind to beta 2 adrenoceptors
At higher concentrations it will also activate alpha 1 receptors causing vasoconstriction
What are the effects of beta 2 adrenoceptors on vascular smooth muscle?
Activating beta 2 adrenoceptors causes vasodilation
Increases cAMP, which activates PKA, which opens potassium channels and inhibits MLCK, which leas to relaxation of smooth muscle
What are the effects of alpha 1 adrenoceptors on vascular smooth muscle?
Activating alpha 1 adrenoceptors causes vasoconstriction
Stimulates IP3 production
Increase in [Ca2+]in from stores and via influx of extracellular Ca2+, leads to contraction of smooth muscle
Describe how beta 2 receptors inhibit excitation contraction
G-protein coupled receptor (Gs) activates adenylate cyclase, which increases cAMP, this activates PKA which inhibits MLCK
MLCK needs to bind to CaM with Ca2+ to phosphorylates myosin head, therefore no contraction
What is the role of local metabolites in blood vessels?
Active tissue produces more metabolites, e.g. adenosine, K+, H+
Local increases in metabolites have a strong vasodilator effect
Metabolites are more important for ensuring adequate perfusion of skeletal and coronary muscle than activation of beta 2 receptors
How are changes in state of system communicated?
Communicated to brain via afferent nerves
E.g. baroreceptors (high pressure side of system), atrial receptors (low pressure side of system)
Alters activity of efferent nerves
Where are baroreceptors?
Nerve ending in carotid sinus and aortic arch which are sensitive to stretch
Increased arterial pressure stretches these receptors
Why is the baroreceptor reflex important?
For maintaining blood pressure over short term
It compensates for moment to moment changes in arterial BP
However, baroreceptors can reset to higher levels with persistent increases in blood pressure
What drugs can act on the ANS?
Sympathomimetics
Adrenoceptor antagonists
Cholinergics
What are the cardiovascular uses of sympathomimetics?
Administration of adrenaline to restore function in cardiac arrest
Beta 1 agonist - dobutamine may be given in cardiogenic shock
Adrenaline administered for anaphylactic shock
What are the other uses of sympathomimetics?
Beta 2 agonist - salbutamol for treatment of asthma
What are alpha adrenoceptor antagonists used for?
Antihypertensive agent - inhibits NA action on vascular smooth muscle alpha 1 receptors - vasodilation
E.g. prazosin
What are beta adrenoceptor antagonists used for?
Propranolol - non selective beta 1/beta 2 antagonist, slows down heart rate and reduces force of contraction and causes bronchoconstriction
Atenolol - selective beta 1 - less risk of bronchoconstriction
What are muscarinic agonists (cholinergics) used for?
Pilocarpine
Used in treatment of glaucoma
Activates constrictor pupillae muscle
What are muscarinic antagonists used for?
Atropine or tropicamide
Increases heart rate, bronchial dilation
Used to dilate pupils for examination of eye