CVS 7 - The Sympathetic Nervous System and the Renin-Angiotensin System Flashcards
Where does the parasympathetic nervous system originate? What about the sympathetic?
Parasympathetic = craniosacral region
Sympathetic = thoracolumbar region
What does increased baroreceptor firing lead to?
A decrease in sympathetic activity - reducing BP and HR
What 2 places are baroreceptors found?
- Aortic arch
2. Carotid arteries
Which neurotransmitter is always used in parasympathetic ?
What about sympathetic?
Ach
Ach, but noradrenaline is used at the effector end of the sympathetic arm.
Where does noradrenaline synthesis occur?
Terminal varicosity - small nodule at the end of sympathetic nerve.
In the sympathetic nervous system, the transmitter is noradrenaline, except in which case?
In the adrenal medulla
Explain the release and reuptake of NA.
Stored in granular vesicles and exocytosed (ACTIVE PROCESS).
NA then reuptaken and removed through 2 mechanisms:
1. Neuronal uptake - goes back to neurone that released it
- Extraneuronal uptake - taken up by extraneuronal cells (effector cell - often VSMC)
In extraneuronal uptake, COMT and MAO are 2 enzymes responsible for subsequent transmitter breakdown.
How are adrenoreceptors subdivided?
They can have 2 effects.
- Excitatory effects on smooth muscle.
- Alpha adrenoreceptor mediates - Relaxant effects on smooth muscle and stimulatory effect on heart
- Beta adrenoreceptor mediated
(Stimulatory means increases force of contraction and HR)
How can Beta-receptors be subdivided?
- Beta 1 = cardiomyocytes, GI tract SMC (stimulates heart)
- Beta 2 = vasculature, bronchi, uterine SMC (relaxes VSMC)
- Beta 3 = Fat cells, potentially GI tract SMC. Involved in thermogenesis (but low in humans as few brown fat cells.) Important in bladder function.
How can Alpha-receptors be subdivided?
- Alpha 1 receptors = post synaptic (many on effector cells). Important mediators of constriction of vessels in response to sympathomimetic amines.
- Alpha 2 = pre synaptic nerve terminal membrane. Activation through released transmitter causes Negative feedback inhibition of further transmitter release. Some Alpha 2 receptors are on VSMC and cause vasoconstriction (like Alpha 1)
Explain coupling of Alpha 1 adrenoreceptors.
- Done via G proteins.
- Receptor activated, which causes PLC activation.
- PIP2 to IP3.
- Leads to Ca influx into cytosol. Contraction ensues.
What is unique about cAMP and the heart?
cAMP is generally a relaxant in Smooth muscle.
In the heart, cAMP is a stimulant.
IF ALPHA 2 RECEPTOR, MUST(!) BE COUPLED WITH BETA 2 RECEPTOR
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cAMP and Calcium are?
Antagonistic, except in cardiac muscle.
Explain alpha 2 and beta 2 receptor coupling.
- Beta receptors are coupled with adenylyl cyclase - increases cAMP levels
- cAMP is a relaxant in smooth muscle, and prevents platelet aggregation.
- Alpha 2 receptors inhibit adenylyl cyclase. This decreases intracellular cAMP and causes contraction in smooth muscle.
Summarise the effects of the major catecholamines on HR.
- Noradrenaline - reflex bradycardia
- Adrenaline - direct increase in heart rate
- Isoprenaline - more direct increase in HR (as it vasodilators - baroreceptors)
Receptor distribution isn’t uniform. Vascular beds in different areas have different receptors so have different vascular responses.
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3 factors which regulate renin release.
- Amount of Na reaching the macula densa (near glomerulus). Less Na = more renin released
- Blood pressure - dependent on pressure within preglomerular vessels. Low BP = more renin released
- Beta(1) receptor activation - sympathetic response in kidneys. More beta receptors activated = more renin released
(all stress situations). Renin release often occurs due to volume loss from circulation
What drugs can be given to decrease blood pressure?
- Angiotensin 2 receptor blockers
- ACE inhibitors - block angiotensin 2 production. (though there are other pathways of Ang 2 production)
- Beta(1) blockers - stop renin release via sympathetic nervous system.
What is an unwanted effect of NSAIDs?
They can increase renin release.
Describe Ang 2 Type 1 receptors. (AT1)
- When activated, increases BP.
- G-protein coupled receptors (Gi and Gq)
- Coupled to phospholipase C and phospholipase A2.
- Located in Blood Vessels, Brain, Adrenals, Kidney, Heart
Describe the rapid pressor responses of Ang 2.
Affects peripheral resistance (rapid pressor response)
- Direct vasoconstriction
- Enhanced action of peripheral NA (increase release, decrease uptake)
- Increased sympathetic discharge
- Release of catecholamines from adrenal gland
Describe the slow pressor response of Ang 2.
Affects renal function (slow pressor response) - occurs over weeks/months
- Increase Na reabsorption in PCT
- Synthesise and release aldosterone from adrenal cortex.
- Altered renal haemodynamics (renal vasoconstriction, enhanced NA effects in kidney)
What are some haemodynamic effects of Ang 2?
- Increased preload and afterload
2. Increased vascular wall tension
What are some non-haemodynamic effects of Ang 2?
- Increased expression of proto-oncogenes
- Increased production of growth factors
- Increased synthesis of ECM proteins
What effects do AT1 receptor antagonists have?
Selectively blocks effects of Ang 2:
Eg. pressor effects, NA stimulation, Aldosterone secretion, renal vasculature, growth promotion on cardiac and vascular tissue are all blocked.
What are chymases?
Family of enzymes that produce Ang 2 from Ang 1 and we don’t have any way of blocking them atm.
Other than Ang 2, what other element stimulates production and release of aldosterone?
K
What effect does aldosterone have on K, Na and H2O?
Lose K.
Retain H2O and Na.
Leads to increased BP
Where are aldosterone receptors present?
Kidneys, Brain, Heart, Blood vessels
Aside from Ang 2 and K, what else affects aldosterone production?
ACTH
What is primary hyperaldosteronism?
Associated with benign tumours of adrenal cortex.
ASSOCIATED WITH HYPERTENSION
What is secondary hyperaldosteronism?
Excessive response of the body in heart and liver failure.
Contrast the 2 phenotypes of hyperaldosteronism.
Primary = High BP + no oedema
Secondary = Low/normal BP + lots of oedema
Compare the Sympathoadreal system and the RAS.
They both work synergistically to maintain extracellular circulatory volume.
Problem is, their effects may lead to hypertension or heart failure.
Both responses to stress (particularly fluid loss)
Activation of both systems leads to:
- Increased BP
- Increased HR
- Increased Na/H2O retention
Mechanisms to reduce fluid loss include:
- Increased coagulation
- Decreased fibrinolysis
- Increased platelet activation
