Lecture 10 Flashcards
What does the ANS (involuntary) regulate/exert control over?
-heart rate, BP, body temp (homeostatic functions)
-co-ordinating the body’s response to exercise and stress
Exerts control over:
-smooth muscle
-exocrine secretion
-rate and force of the contraction of the heart
What are the 2/3 divisions of the ANS + how are they divided into these categories?
Parasympathetic (cranial/sacral origin)
Sympathetic (thoracic/lumbar origin)
Based on anatomical grounds only rather than type of neurotransmitter
(some include the enteric nervous system-surround GI tract-parasympathetic + sympathetic fibres)
Where are the preganglionic cell bodies?
CNS
Difference in length of preganglionic/post ganglionic neurones in sympathetic/parasympathetic neurones:
Sympathetic
- pre:short (synapse in ganglion)
- post:long (innervate target tissue)
Parasympathetic
- pre:long
- post:short (close to/within target tissue)
Can a tissue be innervated by parasympathetic + sympathetic nerves?
Yes.
They often have opposite effects to work together to maintain balance.
(Parasympathetic NS is more dominant under basal conditions, whereas sympathetic activity is increased under stress)
Can sympathetic drive be independently regulated?
Yes. Sympathetic activity to heart can be increased without increasing the activity of the GI tract
(Fight/flight is more generalised activation of sympathetic nervous system)
What does the ANS do/not do in the CVS?
Controls:
- HR
- force of contraction of the heart
- peripheral resistance of blood vessels
Does not:
- initiate electrical activity in the heart
- denervated heart still beats, at a faster rate, as at rest it is normally under influence of vagus nerve (parasympathetic input)
What is the structure of parasympathetic nerves to the heart?
- preganglionic fibres from 10th cranial nerve: Vagus nerve
- synapse with postganglionic cells on epicardial surface/ within walls at AV/SA node (not much innervation of myocardium itself- targets nodes: meaning it can change HR but NOT force of contraction)
- postganglionic cells release ACh
- acts on M2 receptors (G-protein coupled)
- decreases HR, decreases AV node conduction velocity
What do the postganglionic sympathetic fibres innervate?
-from postganglionic fibres from sympathetic trunk
-innervate SA/AV node AND myocardium
Release noradrenaline
Acts on B1 adrenoreceptors (B2/3 adrenoceptors are present in the heart also)
-increasing force of contraction (positive inotropic effect-due to innervation of the myocardium)
-increasing heart rate
How does ANS effect pacemaker potential (slow depolarisation to threshold)?
- sympathetic activity will steepen pacemaker potential (quicker to reach threshold-AP fire faster): NA on beta 1 receptors- G protein, Gs, increase cAMP, HCN channels open allowing Na+ influx= reach TV
- parasympathetic activity will lengthen pacemaker potential (longer to reach threshold): ACh on M2 receptors- G protein, Gi, decreases cAMP + beta/gamma unit increases potassium conductance
How does NA increased force of contraction of heart?
-acts on B1 receptors in myocardium and nodes: (Gs coupled) causing an increase in cAMP-> activates PKA
-phosphorylation of Ca2+ channels (L type), increases Ca2+ entry during plateau phase
-increased uptake of Ca2+ in ER
= increased force of contraction
What is the more common innervation of vessels?
-sympathetic innervation (except specialised tissue e.g. erectile tissue which have parasympathetic)
What type of receptor is present in vascular smooth muscle?
Alpha 1 adrenoceptors
Coronary and skeletal muscle vasculature also have some B2 adrenoceptors
How you how control the diameter of vessels by sympathetic innervation?
-normal vasomotor tone (some sympathetic output (NA) acting on alpha 1 receptors)
(Basal tone allows constriction and dilation)
-relaxation: decrease sympathetic outflow, alllowing vasodilation
-constriction: increase sympathetic output: allowing vasoconstriction
Which blood vessels have B2 adrenoceptors as well as A1, and what is the effect of NA/adrenaline on these?
- skeletal muscle vessels
- myocardium vessels
- liver vessels
-noradrenaline from sympathetic nervous system acts on A1 adrenoceptors to constrict vessel (not all or nothing response- just to regulate BP)
-if you have an increase in circulating adrenaline (fight/flight response), theses act on B2 receptors, adrenaline can also activate A1 receptors at higher concentrations
-B2= dilation
(Predominant effect will be constriction if very high levels of adrenaline, at normal levels they act on B2 receptors for dilation)
How does activating B2 adrenoceptors cause vasodilation?
-increased cAMP (Gs coupled)
-increase in PKA
-opens potassium channels, making them less depolarised-more negative, phosphorylation (pKa) inhibits myosin light chain kinase
= relaxation of smooth muscle
How does activating A1 adrenoceptors cause vasoconstriction?
-stimulate IP3 productions (IP3 receptors on sarcoplasmic reticulum) (Gq)
-increase in Ca2+ from stores/extracellular
= contraction of vascular smooth muscle cells
What are some local metabolites that have a vasodilator effect? (More important than nervous stimulation-B2 receptor activation for adequate perfusion)
-active tissues produce more metabolites
(Adenosine, K+, H+, CO2)
-vasodilator effect to ensure adequate perfusion
What is the overall control of the CVS?
Medullary centres: cardiovascular centres
Afferent nerves:
-baroreceptors: pressure receptors in arterial system (in arteriole system)
Activity from these is detected in control centre which influences the activity coming from sympathetic and vagal nerve (parasympathetic)
-atrial receptors (low pressure side)
Where are baroreceptors found?
-carotid sinus (bulge before the common carotid arteries bifurcate)
-aortic arch
(Increase in blood flow, causes baroreceptors to stretch more= activation to cardiovascular control centres)
What is the baroreceptor reflex?
Increase in arterial BP
-detected by baroreceptors (stretch)
-afferent pathway to medulla: coordinating centre
-efferent pathways from medulla (decrease sympathetic output/increase parasympathetic output)
-reduce HR and force of contraction + relaxation of vessels
= lower arterial BP
Why would a heart beat faster if not innervated?
Because it no longer has the parasympathetic input from the ANS which is the major ANS contribution to the heart.
What is a negative chronotropic effect?
Decreases HR
What is a positive inotropic effect?
Increase in force of contraction
What is the action potential in SA node cells?
- pacemaker potential to threshold (HCN channels)
- upstroke due to Ca2+ channels opening (not due to Na+ opening as they would be inactivated at that membrane potential)
- downstroke due to closing of Ca2+ channels and opening of K+ channels
What is the pacemaker of the heart?
Cells in the SAN
-slow depolarising pacemaker potential
-turning on of slow Na+ conductance (funny current)
-opening of Ca2+ channels
AP firing in the SA node sets the rhythm of the heart
What is the action potential in SAN cells?
- slow depolarising pacemaker potential (funny current) via HCN channels
- opening of fast Ca2+ channels
- closing of Ca2+ and opening of K+ channels
What allows both vasodilation and vasoconstriction to occur?
Basal level of tone (vasomotor tone)
What happens to baroreceptors if there is persistent high BP? (Not just acute high BP)
Baroreceptor reflex re-sets to higher levels with persistent increases in BP
What are sympathomimetics?
(Alpha/beta adrenoceptor agonists)
- exogenous adrenaline (restore function of heart after cardiac arrest/anaphylactic shock causes dilation so vasoconstriction occurs: activates alpha 1 receptors overriding B2)
- Dobutamine (B1 agonist- if in cardiogenic shock)
- salbutamol (B2 agonist- bronchial smooth muscle: vasodilation)
What are adrenoceptor antagonists?
- A1 antagonists (prazosin): anti-hypertensive, inhibits NA action causing vasodilation
- propranolol (non selective against B1/2 antagonist: slows HR and reduces force of contraction it also acts one B2 bronchial smooth muscle= bronchoconstriction)
- atenolol (cardioselective: act on B1, less risk of bronchoconstrictive)
What are cholinergics?
Muscarinic agonists and antagonists
Agonists: pilocarpine (treat glaucoma, activates contraction of pupillae muscle, improving drainage of aqueous humour)
Antagonists: atropine/tropicamide (dilate pupil to examine eye/increases HR/bronchial dilation)
