Session 5 - Autonomic control of CVS and BP

Question 1

recap - arrangments of ganglions in the ANS

Answer 1

Sympathetic - short preganglion - long postganglion to target tissue

parasympathetic - long pre ganglion then a short post ganglion innervated in the target tissue

Question 2

what is the role of the sympathetic system on the heart? what receptors does it act on ?

Answer 2

will lead to increased heart rate and a greater force of contraction by acting on the B1 receptors

Question 3

what is the role of the parasympathetic system on the heart? what receptors does it act on ?

Answer 3

it will decrease the heart rate by acting on the M2 muscarinic receptors

bonus : sympathetic drive to different tissues are independently regulated

Question 4

what does the ANS control of the ANS

Answer 4

ANS controls heart rate and force of contraction and TPR but not initaite the heart beat , SA node does this

Question 5

draw a diagram of the heart that shows ANS input to the heart, with receptors and nerves ect

Answer 5

check against lecture 10

Question 6

how does the ANS effect the pacemaker potential of the SA node ?

Answer 6

sympathetic via the B1 receptors will increase pacemaker potential - noradrenaline binds and increase cAMP via a Gas GPCR - activates PKA - more phosphorylation of ca2+ channels - more Ca2+ enters myocardium - increases the force of contraction

Parasympathetic will decrease the pacemaker potential via M2 receptors - Gai GPCR will decrease cAMP

Question 7

what is the effect of the ANS on vasculature ?

it may help to draw this

Answer 7

ANS in only innervated by sympathetic nerves !!!

they have a1 adrenoreceptors - vasodilation is caused by a decrease in sympathetic output, and vasconstriciton by an increase in sympathetic out put of NA

some vessels also have B2 adrenoceptors
physiological conc - adrenaline binds to B2 and cause vasodilation - increase cAMP —> PKA , opens K+ channels and inhibits MLCK to stop contraction

at pharmocological conc - it will also acitvate A1 receptors to cause vasoconstriction
- stimulates IP3 pathway - more Ca2+ influx - prolonged contraction

Question 8

what is the more important trigger of vasodilation ?

Answer 8

active tissue will produce metabolites such as K+, H+, Adenosine and CO2

this has a very strong vasodilator affect

they are more important than B2 receptors

Question 9

outline how barorecptors work

Answer 9

aortic arch and carotid sinus - stretch to trigger AP - this singals to brain an increase in arterial pressure

this causes brain to trigger bradycardia and vasodilation to counteract this

it is the most important in maintaining BP over SHORT TERM by altering cardiac output

baroreceptors can set to higher levels with a persistent increase in BP - hypertension

Question 10

briefly outline drugs that act on the ANS

just the outline, not the detail

Answer 10

Sympathomimetics

• cardiovascular uses
– administration of adrenaline to restore function in cardiac arrest
– β1 agonist - dobutamine may be given in cardiogenic shock (pump failure)
– adrenaline administered for anaphylactic shock

Adrenoreceptor antagonists
• α-adrenoreceptor antagonists
– α1 antagonists eg prazosin
– anti-hypertensive agent
• inhibits NA action on vascular smooth muscle α1 receptors - vasodilation

• β-adrenoreceptor antagonists
– propranolol
• non-selective β1/β2 antagonist
• slows heart rate and reduces force of contraction (β1) but also acts on bronchial smooth muscle (β2) - bronchoconstriction

Cholinergics
• Muscarinic agonists

• Muscarinic antagonists
– increases heart rate, bronchial
dilation

Question 11

what is hypertension ?

give values for normal and hypertensive BP values

Answer 11

hypertension is a sustained high BP

normal range 90/60mmhg - 120/80

stage 1 more than 140/90
stage 2 more than 160/100
severe hypertension more than 180/110

Question 12

what are the causes of hypertension ?

Answer 12

95% primary hypertension - cause unknown

secondary hyper tension - we know cause and treat by treating the underlying cause

renovascular disease
chronic renal disease
chushings and conns syndrome

hypertension can cause heart failure, MI, Stroke, reniopathy, renal failure, LV hypertrophy

Question 13

draw a diagram explaining the consequences of hypertenison and what causes each thing

Answer 13

check lecture 11

Question 14

the baroreceptor refelx controls short term BP changes

how do we control BP in the long term

Answer 14

general idea is by controlling the sodium balance and hence control the extracellular fuild volume that will follow the Na+ conc

Question 15

what are the 4 pathways that you need to know that control cirvulating volume and hence BP

Answer 15

1. renin-angiotensin-aldosterone system
2. sympathetic nervous system
3. Antidiuretic Hormone (ADH)
4. Atrial Naturetic Hormone (ANP)

Question 16

outline how the renin-angiotensin-aldosterone system works ?

Not vital

Answer 16

• Renin is released from granular cells of juxtaglomerular apparatus (JGA)
• Factors that stimulate renin release:

a) Reduced NaCl delivery to distal tubule
b) Reduced perfusion pressure in the kidney causes the release of renin detected by baroreceptors in afferent arteriole
c) Sympathetic stimulation to JGA increases release of renin

Question 17

draw the angiotensin system and what acts on it , and what it acts on

also include drugs and where they target

Answer 17

check against lecture 11

angiotensin II will go on to cause vasoconstriction, Simulate Na+ (water) resoprtion from the kindey and stimulate aldosterone release from adrenal cortex, which also Simulates Na+ (water) resorption from the kindey, increase thirst sensation - all this is triggered by AT1 and AT2 - angiotensin receptors

Question 18

how does the sympathetic nervous system alter BP ling term ?

Answer 18

High levels of sympathetic stimulation reduce renal blood flow
– Vasoconstriction of arterioles
reduce renal blood flow - decrease Na+ excretion
• Stimulates renin release from JGcells
– leading to increased Ang II levels
– leading to increased aldosterone levels
• increased Na+ reabsorption

Question 19

how does Antidiuretic Hormone (ADH) alter BP long term ?

Answer 19

• Main role is formation of concentrated urine by retaining water to control plasma osmolarity
– Increases water reabsorption in distal nephron

Question 20

how does Atrial Naturetic Hormone (ANP) alter BP long term

Answer 20

Atrial natriuretic peptide (ANP) promotes Na+ excretion
• synthesised and stored in atrial myocytes
• released from atrial cells in response to stretch
– reduced filling of the heart – less stretch – less ANP released - BP can increase again

ANP causes vasodilation, inhibts Na reabsorption

Question 21

how do we treat hypertension ?

Answer 21

non pharma approach

diet
excercise
low Na+ diet
reduce alcohol

Drugs

ACE inhibtors
ANG II receptor agonists/blocker
vasodilators
beta blockers - when other issues as well