8- Sympathetic Nervous And Renin Angiotensin Systems Flashcards
What are the 2 affects of adrenoceptors
“Excitatory effects on smooth muscle, alpha-adrenoceptor mediated”
“Relaxant effects on smooth muscle, stimulatory effects on heart,
beta-adrenoceptor mediated”
What are 5 actions of angiotensin 2
“constricts resistance vessels increasing systemic vascular resistance and arterial pressure
acts on the adrenal cortex to release aldosterone
“stimulates release of ADH from the posterior pituitary,
stimulates thirst centres in brain,
stimulates cardiac and vascular hypertrophic responses
”
What are 2 exceptions to noradrenaline being released at the sympathetic effector neurone
Except in the special case of the adrenal medulla, which acts as a specialised post- ganglionic neuron and releases mainly adrenaline (80%) and noradrenaline (20%) Post-ganglionic fibres to the sweat glands release acetylcholine
Where does NA synthesis occur
the TERMINAL VARICOSITY - this is a small nodule at the end of the sympathetic nerve
Describe the removal of NA from the receptors
Noradrenaline can be removed from the cleft by two methods:
Uptake 1 = goes back to the neurone that released it
Uptake 2 = taken up by extraneuronal cells
• There are TWO enzymes that are responsible for the subsequent breakdown of
the transmitter:
COMT (Catechol-O-Methyl Transferase) MAO (Monoamine Oxidase)
What are the three types of beta adrenoceptor
Beta 1 receptors located on: Cardiomyocytes Smooth muscle of GI tract • Beta 2 receptors located on: Vasculature Bronchi Uterine smooth muscle • Beta 3 receptors were added recently and are found on: Fat cells (brown fat) Possibly on the smooth muscle of the GI tract
What are the 3 types of alpha adrenoceptor
Alpha 1 receptors are located POST-SYNAPTICALLY (predominantly on effector
cells)
o
response to sympathomimetic amines
• Alpha 2 receptors are located on PRE-SYNAPTIC nerve terminal membrane
Their activation by released transmitter causes NEGATIVE FEEDBACK inhibition of further transmitter release
Some are post-synaptic on vascular smooth muscle (these, like alpha 1, cause vasoconstriction)
Describe the coupling of alpha 1 adrenoceptors
This is the signal transduction mechanism of alpha 1 adrenoreceptors via G proteins
• When the receptor is activated, this causes the activation of Phospholipase C
• PLC converts PIP2 to IP3 which leads to a release of calcium from intracellular
stores
• An increase in intracellular calcium in a muscle cell causes CONTRACTION
Describe the coupling of alpha 2 adrenoceptors
Beta receptors are coupled with Adenylate Cyclase which increases the levels of cAMP
• In SMOOTH MUSCLE and PLATELETS = cAMP is an INHIBITOR so it prevents activation, makes smooth muscle RELAX and prevents platelet activation
• In CARDIOMYOCYTES = increase cAMP, like calcium, ACTIVATES the cell - this is unique to cardiomyocytes
• Alpha 2 receptors are also calcium releasing receptors but this is more to do with inhibition of adenylate cyclase
• You reduce intracellular levels of cAMP and therefore oppose the effects of calcium (because calcium isn’t released from intracellular stores)
What are the effects on the heart of NA, A and isoprenaline
Noradrenaline = Reflex Bradycardia Adrenaline = Direct increase in heart rate Isoprenaline = More direct increase in heart rate (not counteracted at all by alpha effects peripherally)
What is NA induced reflex bradycardia
this occurs because
of the baroreceptor loop - vasoconstriction causes an increase in blood pressure which increases the firing frequency of the baroreceptors leading to the deactivation of the sympathetic innervation of the heart and increased activity of the vagus nerve leading to a REDUCED HEART
What 3 elements control the release of renin
Amount of sodium that reaches the macula densa (near the glomerulus) - the less sodium there is, the more renin will be released
Blood Pressure - depends on the pressure within the preglomerular vessels - the lower the blood pressure, the more renin is released
Beta Receptor Activation - sympathetic response in the kidneys
the more beta receptors are activated, the more renin is released
How can drugs be used to influence renin release
Angiotensin II receptors can be blocked
• ACE inhibitors can partially block the production of angiotensin II although there are other pathways of angiotensin II production which are insensitive to ACE inhibitors
• Beta blockers stop renin release in the kidneys
• NSAIDs can increase renin release - this is an unwanted effect
Where are AT1 receptors located
Blood Vessels Brain Adrenals Kidney
Heart
What are the effects of angiotensin 1
Peripheral Resistance - RAPID PRESSOR RESPONSE
Direct vasoconstriction
Enhanced action of peripheral noradrenaline
• The is increase noradrenaline release and decreased uptake Increased sympathetic discharge
• If the sympathetic nervous system and RAS work together they go in the same direction to increase blood pressure
Release of catecholamines from the adrenal gland
• Renal Function - SLOW PRESSOR RESPONSE
This happens over weeks or months
Direct effect is to increase sodium reabsorption in proximal tubule Synthesis and release of aldosterone from the adrenal cortex Altered renal haemodynamics:
• Renal vasoconstriction
• Enhanced noradrenaline effects in the kidney
• 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
