Central control of the cardiovascular system- parasympathetic reflex pathways

Question 1

What is the major parasympathetic nerve ?

Answer 1

vagus nerve (X)
- innervates many organs within the body
80% of signals are from the organs to the brain - monitoring internal environment
20% of signals are from the brain to organs

Question 2

Where are baroreceptors found and where do they project to ?

Answer 2

present in the aortic arch- send signals off into the aortic nerve to the nodose ganglion and then onto CNS by the vagal nerve
present in the carotid sinus - sends off signal to the petrosal ganglion which then goes onto CNS via the glossopharyngeal nerve

Question 3

What causes changes in BP?

Answer 3

changes in baroreceptor activity
increased pressure= increased action potential firing
decreased pressure= decreased action potential firing

Question 4

What did the working heart-brainstem model demonstrate about the baroreflex and how was it carried out ?

Answer 4

in this model no anaesthetic is required so brainstem is still present so autonomic reflexes and respiratory control are all retained
animals were perfused with an artificial fluid to increase perfusion pressure causing a reflex decline in HR

Question 5

What happened when atropine (parasympathetic blocker) was applied to the preparation?

Answer 5

the baroreflex response was stopped therefore this indicated that the baroreflex decline in HR is mediated through the vagus nerve as the vagus being activated reduces HR

Question 6

Why did they remove the nodose ganglion ?

Answer 6

they removed it to look for mRNA for ion channels that are mechano-sensitive
ASICs- 5 different types, ASIC2b more highly expressed
thought that these channels would be good for looking at mechano changes

Question 7

What control did they use to test the expression of asic2a and 2b channels in the nodose ganglion ?

Answer 7

with immunohistochemistry antibodies may detect something else so it is important to carry out a control
the best control is to produce asic 2 KOs and there should be no labelling

Question 8

What did other immunohistochemical experiments show ?

Answer 8

showed that other ASIC channels colocalise with ASIC2 in the NG and baroreceptive cells

Question 9

What occurred when ASIC2 was KO ?

Answer 9

MAP increased
HR increased
Locomotor activity reduced
the increased MAP and HR indicates that ASIC2 is involved in cardiac control
when it is KO the baroreceptors cant sense changes in BP so sympathetic activity predominates
cutting the baroreceptive nerve induces the same responses

Question 10

How is baroreflex sensitivity expressed?

Answer 10

expressed as the change in PI (pulse interval) per change in systolic blood pressure

Question 11

What happens to the baroreflex sensitivity in ASIC2 KO mice?

Answer 11

baroreflex sensitivity is significantly reduced compared to WT - it is reduced because it couldn’t sense changes in BP

Question 12

What is baroreflex sensitivity like in WT mice ?

Answer 12

normally when blood pressure increases you get a slowing of the heart but in the KO the slowing of heart doesn’t occur as much due to less sensitivity towards change in BP

Question 13

What happened to baroreflex engagement in the ASIC2 KO mice?

Answer 13

number of sequences per 1000 beats that reflect the frequency of engagement of the baroreflex during spontaneous fluctuations in arterial pressure is significantly lower in KO

Question 14

What happens to WT and ASIC2 KO when atropine is applied ?

Answer 14

atropine blocks parasympathetic side
WT showed an increased HR but in the ASIC2 KO HR wasn’t increased barely at all because there was no baroreceptive inputs

Question 15

What happens to WT and ASIC2 KO when propanolol is applied ?

Answer 15

propranolol blocks sympathetic drive by blocking beta adrenoreceptors
WT demonstrate a reduced HR but the ASIC2 KO demonstrated a much greater decrease in HR

Question 16

Whats when the ganglion is blocked upon WT and ASIC2 KO mice?

Answer 16

by blocking the ganglion, all autonomic innervation is removed
WT had a reduced MAP but the ASIC2 KO had a much larger decreased MAP
this indicates that sympathetic activity is greater upon the ASIC2 KO because there is a much bigger decrease in BP

Question 17

What happened when the aortic depressor nerve was stimulated?

Answer 17

aortic depressor nerve comes from the aortic arch and goes into vagus nerve
both WT and ASIC2 KO mice had similar results, both increased bp
the KO had analogous effects to the WT because stimulating the nerve directly, bypasses the mechano-sensitive activity therefore the effects are the same as WT

Question 18

What neuronal tracer did they inject into the aortic arch and what did it show?

Answer 18

DiI is a retrograde tracer which was injected into the aortic arch
it travelled retrogradely to cells in the nodose ganglion
they then took the nodose ganglion out and did patch clamp recordings from DiI labelled cells, they proded these cells to see if they responded to mechanical stimulation- the DiI labelled cells responded more than non-DiI labelled cells

Question 19

When they looked at the DiI labelled cells from the nodose ganglion what was seen ?

Answer 19

these cells expressed more ASIC2 therefore this indicates that baroreceptor cells have more ASIC2

Question 20

What results were shown by proding cells that have overexpression of ASIC2, WT and ASIC2 KO?

Answer 20

overexpressed- these cells were hypersensitive and therefore they responded more robustly to the mechanical stimulation compared to WT
wt- responded to mechanical stimulation but not as much as overexpressed cells
KO- didn’t respond as strongly as WT

Question 21

What happens to BP when sodium nitroprusside is applied and what happens when noradrenaline is applied in WT and in ASIC2 KO?

Answer 21

WT- sodium nitroprusside reduces BP as it reduces aortic nerve activity whereas noradrenaline increased BP as it increased the activity of the aortic nerve
ASIC2 KO- sodium nitroprusside reduced bp but not as much as WT as aortic nerve activity wasn’t as active as the cells are not as responsive to changes in BP. Noradrenaline increased the BP..

Question 22

What clinical benefit is highlighted by these ASIC2 KO cells?

Answer 22

demonstrates that if you manipulate these ion channels you might be able to alter the sensitivity of baroreceptors and therefore this could be important for treating hypotension or heart failure

Question 23

What did they do to determine where the baroreceptor cells project to in the CNS and what was shown ?

Answer 23

they took the baroreceptor nerve and cut it and then dipped it in HRP neuronal tracer
this tracer was taken up by nerves and across nodose ganglion and into other nerve terminal and it showed that most of the neurons were in the NTS in the brainstem

Question 24

When determining where baroreceptors project to in the CNS why did they use rats?

Answer 24

because they thought aortic nerve are considered to only have baroreceptive functions whereas the carotid sinus has both baroreceptive and chemoreceptive functions but this may not actually be the case

Question 25

What was determined when they recorded from the neurones in the NTS?

Answer 25

it demonstrated that neurones in the NTS dont have a purely baroreceptive function as the cells were all intermingling which responded to chemoreceptive, baroreceptive ad other effects

Question 26

How did they identify baroreceptive neurones in the NTS?

Answer 26

using heart-brainstain prep they patch clamped the NTS and identified baroreceptive neurones by increasing the pressure
increasing the pressure increased baroreceptive firing

Question 27

Other than the NTS where else did baroreceptive cells project to ?

Answer 27

many projected to other NTS neurones telling them what was happening
also projected to dorsal vagal nucleus and nucleus ambiguus

Question 28

What was shown when they retrogradely labelled neurones from the heart and stimulated the NTS?

Answer 28

labelled nerves retrogadely from the heart and then electrically stimulated the NTS, showed monosynaptic projections from NTS and cardiac vagal neurones
stimulating the NTS activates vagal neurones within the nucleus ambiguus
- this study stated that they recorded from NA neurones but most cardiac vagal neurones don’t lie in that area so it is thought that actually they were recording from neurones that the tracer had spilled over into the external formation

Question 29

Where are most cardiac vagal neurones located?

Answer 29

most are in the external formation

Question 30

Where are the cardiac ganglion plexuses?

Answer 30

1) one is present in the vicinity of the SAN
2) one is present in the region of the AVN
3) one is present where the lower pulmonary veins enter the left atrium
each of these ganglion plexuses contains many individual ganglia interconnected by nerve bundles

Question 31

What did confocal microscopy demonstrate about innervation of cardiac ganglia?

Answer 31

the dorsal vagal motor neurons and nucleus ambiguus neurones innervate the cardiac ganglia
both these types of neurones innervate the same ganglia but they innervate separate subpopulations of principal neurones
the axons on the contralateral sides enter via different regions to the cardiac ganglia and they tend to innervate the neurones nearest to their point of entry

Question 32

What is the pressor area of the RVLM regulated by ?

Answer 32

regulated by inhibitory inputs from the CVLM

Question 33

What regulates the CVLM?

Answer 33

regulated by excitatory inputs from baroreceptors via an interconnected synapse in NTS