Lecture 14: The Role of SNS in disease

Question 1

Describe the baroreflex baroreceptors;

Answer 1

Baroreceptors for the arterial baroreflex are found;

• Carotid sinus (carotid sinus nerve, CN IX)
• Aortic arch (Aortic Depressive nerve, CN V)

Question 2

What happens to rate of baroreceptor response when blood pressure increases?

Answer 2

Increase BP = Increase firing = Decrease SNA = decreased HR

also dont forget!

Increased PNA; = decreased HR

Question 3

Describe the carotid sinus firing, MABP curve;

Answer 3

Sigmoidal
= No firing at low pressures
= High firing at high pressures but does not increase beyond x

Question 4

Describe carotid sinus firing in the cardiac cycle;

Answer 4

Systole = increased firing
Diastole = decreased firing

Thus bursts of sympathetic drive occur at specific points in the cardiac cycle

Question 5

Describe the HR vs BP curve;

Answer 5

Inverse of MABP vs Carotid sinus firing

• sigmoidal but gets lower as BP (X) gets larger
• In HF patients their max HR is already lowered and low HR is raised slightly.

Question 6

In disease states what happens to the baroreflex?

Answer 6

In disease states that baroreflex is altered

• altered SNA
• In HF there is down regulation of B1

Question 7

Whats the function of the carotid sinus nerve;

Answer 7

Carrys information on;

• BP
• Chemoreceptor info (pH, pO2, pCO2)

(as does the aortic bodies)

Question 8

Describe what happens when pO2 is lwoered;

Answer 8

Decreased pO2=

• Increased respiration and tidal volume
• Increased HR and CO

Question 9

Describe SNA in disease states;

Study 4/7 for SNA

Answer 9

Disease states increase SNA

• To the muscles (but not skin)
  i. e
• Essential hypertension
• Obesity
• Congestive HF

Question 10

Is increases SNA part of the development of disease i.e hypertension or an established phase?

Study 5/7 for SNA

Answer 10

They think increased SNA is part of the development of disease.

b/c

Normotension patients with familial hypertension have elevated SNA prior to the disease setting in

also

Obese patients with sleep apnea have increased SNA

Question 11

Whats a hindrance in studying humans SNA?

Answer 11

Only nerve activity directly measurable in humans is skin and muscle SNA

Question 12

What technique is used to infer SNA?

Answer 12

The spillover technique

Question 13

Describe the spillover technique;

Answer 13

Can measure NE release and found that in hypertension there is increased spillover tot he heart and kidney (where excess to normal NE is found)

Question 14

What did they fin using the spillover tehcnique?

Answer 14

The larger the spillover the lower the survival rates per a year.

Question 15

What targets SNA?

Answer 15

A large number of treatments target SNA

i.e alpha and beta blockers

Question 16

Describe SNA and heart failure;

Answer 16

A central factor of this disease is an increase in neurohormonal drive to the CVS

Question 17

Describe the spillover in HF;

Study 6/7 for SNA

Answer 17

10x and 2x fold in NE spillover to he heart and kidneys respectively in HF

(only moderate to severe HF has increased SNA to kidneys)

And increased SNA activity to muscles in HF

Question 18

What are the detrimental effects of increase SNA in HF;

Answer 18

Initially thought to be beneficial by having inotropic action to the failing myocardium but at a cost of;

• NE toxicity of myocyte
• Downregualtion of cardiac Beta receptors
• Coronary vasoconstriction (alpha 1)
• NPY release
• Arrhythmogenesis
• Sudden death

Question 19

What does increased spillover predict?

Answer 19

Increased spillover in HF predicts patients survival

Beta blockers prevent mortality

Question 20

What else occurs in heart failure that is bad?

Answer 20

There is reduced Sympathetic fibres to the heart

Question 21

What drives the increase in SNA?

Answer 21

• Altered baroreflex
• Altered cardiopulmonary reflex
• Cardiac afferent reflex
• Central ANG2 and NO

Question 22

What is the role of chemoreceptor reflex in mediating the increased SNA to the heart;

Answer 22

Atrial chemoreceptors play a role in muscle and renal increased SNA

Question 23

Whats their hypothesis regarding chemoreceptor reflex and SNA?

Study 7/7 for SNA

Answer 23

Hypothesis; Chemoreceptor deactivation using 100% oxygen will decrease SNA in HF animals

i.e in HF there is increased chemoreceptor activity but no change in pH, pCO2,pO2, thus there must be overreactive receptors for pO2

Unsure why this happens

Question 24

Whats the medication compliance in HF patients?

Answer 24

It is estimated that 30% of HF patients dont medicate

Question 25

What are the fundamental features of SNA?

Answer 25

• SNA always active and changing
• SNA is differentially regulated to different organs
• The activation of SNA during disease is differential
• High levels of CSNA and RSNA are bad for you

Question 26

What was the concluding question?

Answer 26

Would pacing the heart with respiration improve HF?