CVS 8 - The sympathetic nervous system and RAAS Flashcards
Where the baroreceptors located?
Carotid sinus + aortic arch
What happens if there is an increase in baroreceptor firing?
This decrease the discharge of the sympathetic nervous system leading to a decrease in blood pressure and heart rate.
What neurotransmitter do all parasympathetic neurones release?
ACh
What is the most common neurotransmitter released at the effector end of a sympathetic neurone and what are some exceptions?
Noradrenaline
Exceptions: the adrenal medulla acts as a specialised post-ganglionic neurone as the chromaffin cells produce mainly adrenaline (80%) and noradrenaline. Sympathetic neurons to sweat glands release acetylcholine.
Describe the two methods of uptake of catecholamines from the synaptic cleft and state the two enzymes involved in their breakdown.
They are either taken up into the presynaptic neuron that released them or into extraneuronal tissue.
Enzymes = Monoamine Oxidase (MAO) and Catechol-O Methyltransferase (COMT)
How are the adrenorecepors divided?
Alpha - excitatory on smooth muscle cells
Beta - relaxant on smooth muscle cells + stimulatory on heart
Where are beta 1 receptors located?
Heart
Muscle
GI tract
Where are beta 2 receptors located?
Bronchi
Vasculature
Uterine Smooth Muscle
Where are alpha 1 receptors located and what is their main function?
Post-synaptic membrane - they mediate VASOCONSTRICTION
Where are alpha 2 receptors located and what is their function?
They are located on the presynaptic membrane and are involved in negative feedback.
Some are post-synaptic on smooth muscle cells and cause VASOCONSTRICTION (like alpha 1 cells)
Describe the structure of the adrenoreceptors.
Alpha 1 = Gq protein linked (PLC)
Alpha 2 + Beta 1 + Beta 2 = Adenylate Cyclase (G alpha)
How do the effects of cAMP on smooth muscle, platelets and cardiomyocytes vary?
Increasing cAMP is:
INHIBITORY = smooth muscle + platelets
STIMULATORY = cardiomyocytes (unique, because increases IC calcium so contractility)
Which adrenoreceptors do noradrenaline and adrenaline act on?
Noradrenaline = a1 + a2 + b1 Adrenaline = ALL the adrenoreceptors (so a1 a2 b1 b2)
State two synthetic compounds that can act on the adrenoreceptors and which adrenoreceptors do they act on?
Isoprenaline = b1 + b2 (pure beta agonist) Phenylephrine = a1
What is the effect of a) noradrenaline, b) adrenaline and c) isoprenaline on systolic BP, diastolic BP, mean BP and heart rate?
Noradrenaline = increase, increase, increase, decrease Adrenaline = increase, decrease, increase, increase Isoprenaline = increase, decrease, same, increase
What three elements regulate renin release?
Amount of sodium reaching the macula densa cells
Blood pressure in the pre-glomerular vessels
Sympathetic activity can increase renin release through beta1 receptors
Describe ways in which the renin-angiotensin system can be inhibited.
ACE inhibitors - prevent conversion of angiotensin I to angiotensin II
Angiotensin II type I receptors (AT1) antagonists - prevent angiotensin II from exerting its effects
Beta blockers - prevent renin release
What type of receptor is an Angiotensin II Type 1 (AT1) receptor?
G protein coupled receptors (Gi and Gq)
What is the rapid pressor response of angiotensin II?
Direct vasoconstriction
Enhanced action of peripheral noradrenaline
Increased sympathetic discharge
Release of catecholamines from adrenal medulla
What is the slow pressor response of angiotensin II?
Happens over weeks or months
Increased sodium reabsorption
Increased release of aldosterone
Altered renal haemodynamics - renal vasoconstriction + enhanced noradrenaline effects in the kidney
Describe the effects of angiotensin II on the heart.
Increased preload and afterload
Increased vascular wall tension
Why don’t ACE inhibitors completely wipe out angiotensin II production?
There is another pathway that converts angiotensin I in to angiotensin II.
This reaction is carried out by CHYMASES
What is another effect of ACE inhibitors other than reducing angiotensin II?
Reduce the breakdown of bradykinin
What effect do angiotensin II type 1 receptor antagonists have?
Selectively blocks the effects of angiotensin II
It has NO effects on the bradykinin system because ACE is working perfectly fine
What is the effect of aldosterone?
Increase Na+ reabsorption
Increase K+ and H+ secretion
What are two main stimuli for aldosterone release?
Angiotensin II
Increased Potassium
What are some harmful effects of aldosterone release?
Hypertension -------> Heart Failure Primary Hyperaldosteronism (associated with benign tumours of the adrenal cortex) = HYPERTENSION + no oedema Secondary Hyperaldosteronism (excessive response of the body in heart failure and liver failure) = Low/Normal blood pressure + SEVERE OEDEMA
What is a potent stimulus for the sympatho-adrenal and renin-angiotensin systems?
FLUID LOSS (e.g. severe haemorrhage)
