9 Sympathetic Nervous and Angiotensin System Flashcards
Q: What makes up the ANS?
A: sympathetic NS and parasympathetic NS
both interlink but originate from different nerves
Q: What regulates the SNS? Where does it originate? Include diagram.
A: REFER
outflow from SNS mainly occurs from thoracic spinal cord (T 1 to 5) and lower end (T12 to L3)
Q: What’s the structure of the SNS? (3)
A: 2 ganglionic neurones- pre and post
has ganglia along side spinal cord (intermediary stage for SNS) = sympathetic trunk
continues to reach larger ganglia directly connected in abdomen eg as solar plexus or menesteric ganglia (closely related to gut)
Q: Where does a lot of autonomic cardiovascular control come from? Describe overall control. (7)
A: baroreceptors - pick up on pressure changes and in terms of blood vessel pick up on changes in distension
- pressurised blood vessel expands more and is picked up by BR in the carotid sinus and aortic arch
- -> go to hypothalamic autonomic centre
OUTFLOW HAS 2 OPTIONS
- -> 1. to sinus node via vagus nerve through PNS -> slows heart by reducing contractility
- -> 2. to brainstem: solitary tract nucleus -> through spinal cord
- -> pre ganglionic neuron
- -> sympathetic post ganglionic neuron
- -> dilates vessels -> reduces pressure (particularly through receptors: arteriolar constriction alpha1 receptors)
Q: What are autonomic effector nerves? Compare the 2 types. (3)
A: nerves that carry out actions of both halves of the ANS
- both have 2 ganglia
- cholinergic intermediary step (ACh NT)
- (paravertebral) sympathetic chain ganglia -> has adrenaline NT between post ganglionic neuron and target
- parasympathetic ganglia in or near effector organs -> has ACh NT between post ganglionic neuron and target
Q: What does a postganglionic sympathetic neuron particularly connect to? causes? (2) Balance? (4)
A: blood vessels
-> causing constriction and in absence= vasodilation
finally balanced system
- neuron will stop release of NT: Norepinephrine/ noradrenaline and adrenaline
- will be taken up and broken down via to pathways
- taken up by neuron that released it (terminal variscosity) and metabolised by intraneuronally by monoamine oxidase (MAO)
- taken up by target and metabolised by catechol-o-methyl transferase (COMT)
=> result= stops NT continuously stimulating target
Q: What are the 2 main catecholamines? Compare structure. Where are they made? how? (5)
A: Norepinephrine/noradrenaline and adrenaline : benzene ring with 2 hydroxyl groups- differ in third side chain (adrenaline has larger one)
terminal variscosity: type of synapse in which the presynaptic cell releases neurotransmitter at a series of swellings along the axon (small expansion of neuron)
- tyrosine enter TV
- converted-> DOPA
- DOPA-> converted -> dopamine
- enters vesicle in TV
- converted-> NA
Q: Describe the release of a neurotransmitter. (5)
A: terminal varicosity contains granular vesicle containing NT usually NA
- fusion of vesicle with varicosity membrane
- exocytic channel opens
- vesicle contents are expelled by exocytosis (energy requiring process/ATP)
- reuptake (of some)
- biosynthesis replenishes granular contents
Q: Describe the removal of a NT eg NA from a neuroeffector junction.
A: 1. neuronal uptake into varicosity (reused or broken down by MAO= monoamine oxidase)
- extra neuronal uptake by effector cell (usually vascular smooth muscle) -> broken down by MAO or catechol-o-methyl transferase (COMT))
Q: What are the 2 subdivisions of adrenoreceptors?
A: Two groups of effects:
(1) Excitatory effects on smooth muscle-> increases its conductivity
- alpha-adrenoceptor-mediated
(2) Relaxant effects on smooth muscle, stimulatory effects on heart
- beta-adrenoceptor-mediated
Q: What are the subdivisions of beta-adrenoreceptors? (3) Include location (2,3,3).
A: Beta 1-adrenoceptors located on
- cardiac muscle (mainly has blocking effects)
- smooth muscle of the gastrointestinal tract
Beta 2-adrenoceptors located on
-bronchial, vascular and uterine smooth muscle
Beta 3-adrenoceptors found on
- (brown) fat cells-> reduces body fat in animals (when stimulated cause the production of heat)= Involved in thermogenesis but few in humans.
- possibly on smooth muscle of gastrointestinal tract.
- Important in bladder function:
mirabegron
Q: What are the subdivisions of alpha-adrenoreceptors? (2) Include location (1,1) and function (1,2).
A: Alpha 1-adrenoceptors located
- post-synaptically i.e. predominantly on effector cells eg smooth muscle
- important in mediating constriction of resistance vessels in response to sympathomimetic amines in CVS
Alpha 2 -adrenoceptors located
- on presynaptic nerve terminal membrane
- their activation by released transmitter causes negative feedback inhibition of further transmitter release
- some are post-synaptic on vascular smooth muscle
=> 2 work in both ways: can inhibit NT release or produce effects similar to 1 and cause vasoconstriction
Q: Describe the coupling of adrenoreceptors- include how they vary. Compare 3 effects.
A: coupling of alpha 1 adrenoceptors
- based on g proteins that activate PLC enzyme on cell membrane
- causes release of IP3
- intracellular calcium stores are released
- cause platelet activation in platelets, vasc smooth constriction (get a stronger effect with VGCaC), heart activation
coupling of beta and alpha 2 receptors
- based on g proteins that cause release of cAMP
- effects are relaxant in smooth muscle of gut wall
- anti platelet activation
- BUT stimulate heart (increase contractility)
Q: Name 5 molecules that can probe the adrenergic NS. What are they all? What receptors do they bind to?
A: catecholamines that activate adrenoceptors
natural
- noradrenaline - alpha 1, alpha 2, beta 1
- adrenaline - alpha 1, alpha 2, beta 1, beta 2 (all)
- dopamine - weak effects on alpha 1 and beta 2-> has own receptors = particularly important in kidneys
synthetic
- isoprenaline - beta 1 and beta 2
- phenylephrine - alpha 1 (vasoconstricter)
Q: Where does noradrenaline come from? adrenaline? What is dopamine?
A: mainly sympathetic nerves and to some extent from medulla of adrenal gland
medulla of adrenal gland
precursor for the catecholamines
Q: In what situation is adrenaline important? explain.
A: anaphylaxis
Anaphylaxis is an extreme allergic reaction where you get release of vasodilators and bronchoconstriction - adrenaline (as it binds to all adrenoreceptors) will activate all the receptors you need to counteract this (increase bp and dilate bronchi)
Q: Complete table for the cardiovascular effects of catecholamines in man: 10 microg/min infused i.v.
catecholamine
- noradrenaline
- adrenaline
- isoprenaline
systolic bp
diastolic bp
mean bp
heart rate
A: diastolic bp is more determined by vasodilation
NA
- ^^^ systolic BP as causes heart to conduct more strongly and increases vascular resistance
- ^^ diastolic BP - not a massive effect as little effect as a vasoconstricter
- ^^ mean BP
- \/ heart rate: NA causes vasoconstriction = increase bp = baroreceptors detect = tend to slow heart by vagus nerve/para sympa)
A
- ^^
- \/ as dilates blood vessels
- ^ mainly due to systolic effects
I
- ^ weak effect- activates heart but will not constrict blood vessels
- \/ \/ will dilate many blood vessels
- \/ or -> : nothing in particular
- ^^
Q: Response of major vascular beds to catecholamines.
Vascular bed
- skin
- visceral (gut)
- renal
- coronary
- skeletal muscle
Receptor? Effects of NA? AD? ISO?
A: skin, alpha, NA= constrict, AD= constrict, ISO=none
visceral, alpha, NA= constrict, AD= constrict, ISO=none (dil.)
renal, alpha (beta), NA= constrict, AD= constrict, ISO=none (dil.)
coronary, alpha, beta 1, dilate, dilate, dilate
skeletal muscle, alpha, beta 2, constrict, dilate, dilate
Q: What’s the focus of the renin angiotensin system? Control? Function?
A: kidneys- release renin and cause angiotensin cascade
cells that release renin are partly under control of SNS through beta1 receptors
helps maintain bp
Q: What is the biosynthetic pathway for angiotensin II? (3)
A: angiotensinogen (made in liver) -> angiotensin I
E: renin= large protease
angiotensin I -> angiotensin II
E: angiotensin converting enzyme (ACE)
ANG II inhibits more renin release
angiotensin II -> angiotensin III (doesn’t do much)
E: aminopeptidase (degradation)
Q: What are the 3 factors regulated renin release? What are they all a result of? Cells that make renin?
A: renin release stimulated by
- decreased sodium reaching cells (NaCl reabsorption at macula densa)
- decreased bp (in preglomerular vessels)
- B1 receptor activation in kidney
increased arterial blood pressure
juxtaglomerular cells (JG cells, or granular cells) are cells -specialided smooth muscle cells mainly in the walls of the afferent arterioles, and some in the efferent arterioles, that deliver blood to the glomerulus
Q: What happens to renin production when blood pressure goes down? (3)
A: lower arterial bp =
less sodium reaching cells//NaCl reabsorption at macula densa
less bp (in preglomerular vessels)
B1 receptor activation in kidney (due to increased sympathetic tone)
Q: Give examples of pharmacologic manipulation of renin release. (5)
A: -loop diuretics= tend to increase renin release as you get less Na going to cells
- NSAID= cause Na water retention
- ACE inhibitor= less angiotensin
- AT1 blockers= effects of angiotensin aren’t expressed
- beta 1 blockers prevent kidney renin release
Q: Where are angiotensin II receptors found? (5) What is it? (2) What does activation do? how? (2) side?
A: located everywhere- blood vessels, brain, adrenal, kidney, heart
- g protein couples; Gi (inhibits adenyl cyclase) and Gq (activate PLC)
- also couples with phospholipase A2
works to increase BP
- rapid pressor response (peripheral resistance)
- slow pressor response (renal function)
changes in cardiovascular structure
Q: What’s the effect of angiotensin II on peripheral resistance? Direct effect? Others? (5)
A: RAPID PRESSOR RESPONSE= increases bp in mins
- Direct vasoconstriction
- Enhanced action of peripheral noradrenaline
- increased NE release
- decreased NE uptake
- Increased sympathetic discharge (CNS)
- release of catecholamines from the adrenal gland
Q: What’s the effect of angiotensin II on renal function? Direct effect? Others? (4)
A: SLOW PRESSOR RESPONSE = increases bp over weeks or months
- Direct effect is to increase sodium reabsorption in proximal tubule = increases water retention
- Synthesis and release of aldosterone from the adrenal cortex
- Altered renal haemodynamics:
- Renal vasoconstriction
- Enhanced noradrenaline effects in the kidney
Q: What’s the effect of angiotensin II on cardiovascular structure? 2 types of effect? Describe (2,3). What does this lead to? (2)
A: Vascular and Cardiac Hypertrophy and Remodelling
Haemodynamic Effects
- Increased preload and afterload
- Increased vascular wall tension
Non-Haemodynamic Effects
- Increased expression of proto-oncogenes
- Increased production of growth factors
- Increased synthesis of extracellular matrix proteins
larger heart but not more efficient and blood vessel thickening-> where they don’t dilate
Q: What’s the problem with using ACE? Solution?
A: chymase= family of enzymes that can cause the conversion of ANG I to II (even from angiotensinogen) -> no change in effect by using ACE inhib
means that ACE inhibitor does not completely inhibit process
solution= target AT1 receptor (AT2 receptor exists)
Q: Describe the pharmacology of ACE inhibition. (3)
A: ACE is also known as kininase II and has function of degrading bradykinin
-> bradykinin is a vasidilator/inflam and preventing its degradation= causes vasodilation and decreased blood pressure
inhibitor inhibits that function and ANG I to II -> prevents ANG II increasing BP = decreases BP
Q: What are the actions of angiotensin II type 1 receptor antagonists? (9)
A: -No effects on the bradykinin system
- Selectively block these effects of the Angiotensin II:
- Pressor effects
- Stimulation of noradrenaline system
- Secretion of aldosterone
- Effects on renal vasculature
- Growth-promoting effects of cardiac and vascular tissue
- Uricosuric effect
- You can get angiooedema - this is similar to anaphylaxis but not as bad - it was thought to be due to the accumulation of bradykinin
Q: What’s the role of aldosterone? Result? (3)
A: maintain body content of Na+, K+ (and H2O)
- increased Na+ retention (and H2O)
- increased K+ excretion (and H+ excretion)
can result in slight alkalosis
Q: What controls the release of aldosterone? (3) Where are aldosterone receptors? (3)
A: released caused by
- Increased Potassium
- Angiotensin II
- Minor effect from ACTH
used to be thought that aldosterone only works in the kidneys but it has recently been discovered that there are aldosterone receptors in the brain, heart and blood vessels
Q: What are the Pathophysiologic Effects of Aldosterone in Cardiovascular Disease? (9)
A: -myocardial fibrosis and necrosis
- inflammation, vascular fibrosis and injury
- prothrombotic effects, impaired fibrinolysis
- central hypertensive effects
- endothelial dysfunction
- autonomic dysfunction: catecholamine potentiation, decreased heart rate variability
- potassium and magnesium loss
- ventricular arythmias
- sodium retention
gives CV disease
Q: What can cause too much aldosterone? (2) Compare.
A: Primary Hyperaldosteronism - associated with benign tumours of the adrenal cortex - this is associated with hypertension
Secondary Hyperaldosteronism - excessive response of the body in heart failure and liver failure - the phenotype is completely different
Phenotypes of Hyperaldosteronism:
Primary = high blood pressure + NO oedema
Secondary = low/normal blood pressure + LOTS of oedema
Q: What’s the relationship between the sympathoadrenal system and renin angiotensin system? What do they cause? (6) Which ones lead to change in fluid? what’s the change?
A: both can be triggered by stress// aim- MAINTAINING EXTRACELLULAR CIRCULATORY VOLUME and bp
cause
- increase bp
- increased heart rate (HR)
- increased sodium and water retention
- increased coagulation
- decreased fibrinolysis
- increased platelet activation (increased thrombosis formation)
effects to decrease fluid loss:
- Increased Coagulation
- Decreased Fibrinolysis
- Increased Platelet Activation
