Lecture 17; Integration

Question 1

Are textbooks correct?

Answer 1

They present theory! so will present alternative theories today

Question 2

What is the set point of blood pressure regulation determined by?

Answer 2

Because kidneys control the long term blood pressure regulation it is believed that the pressure natriuresis equilibrium point controls blood pressure i.e the MABP when renal outflow of water / salt is x1

Question 3

Whats the alternative theory to blood pressure being in control of long term blood pressure regulation;

Answer 3

CNS autoregulation playing a role in blood pressure “set point”

Question 4

Describe what factors are monitored in the brain;

Answer 4

Hormones
Osmolarity
Autonomic reflexes

CEREBRAL PERFUSION PRESSURE

Efferent = SNA

Not suggesting that blood pressure is entirely maintained by brain, renal influence too!

Doesnt know exactly what brain measures

Question 5

Describe what the efferent outputs of the brain are;

Answer 5

SNA

• Heart rate contractility (CO)
• Renin - blood volume + thirst, salt, AVP (sensed in brain) (CO)
• Capacitance (CO)
• Resistance (TPR)

CO x TPR = BP

Question 6

Describe how lifestyle influences SNA;

Answer 6

Lifestyle increases blood pressure as you age

Question 7

What is found when measuring muscle SNA

Answer 7

That there is a nice correlation between SNA and blood pressure

Unknown if causal or secondary

Question 8

Define spillover;

Answer 8

How much NE is being produced by the kidney and not being taken up.

Question 9

What does renal spillover indicate;

Answer 9

Renal spillover was quite high in young patients with essential hypertension

Good correlation

Thus there is some component of ‘neurogenic hypertension’ in these young patients

Old people have CV remodelling so harder to measure / indicate

Question 10

What happens as a general rule when you cut renal sympathetic nerves?

Answer 10

10mmHg drop in blood pressure

Question 11

What does King suggest about renal SNA;

Answer 11

Renal SNA is not essential as if you cut these nerves then administer ANG 2 it does not stop the development of hypertension

Question 12

What happened when KING cut the gut sympathetic nerve;

Answer 12

This prevented the development of hypertension therefore its the volume of nerves cut not just the renal nerves.

(thus saying that SNA plays a role in hypertension)

Question 13

What does a recent review of SNA suggest?

Answer 13

That as you cut the SNA to vascular beds it drops the the blood pressure by 10mmHg each time.

Question 14

Describe the summery of long term control of MABP

Answer 14

1) Be non-adaptive
2) affect renal function
3) Likely to involve neural and humoral interactions

i.e ANG 2, acting centrally to influence renal SNA, which in turn influences SNA

Question 15

Describe what is recommended for treatment of hypertension in terms of lifestyle changes;

Answer 15

1. Weight Reduction
2. Moderation of alcohol
3. Diet - high fruit, veges, low fat
4. Salt restriction
5. Regular exercise
6. Smoking cessation

Question 16

What evidence indicates weight loss is good for hypertension treatment?

Answer 16

A study indicated that 5kg weight loss = 4mmHg systolic and diastolic drop in BP

Question 17

Whats the ABCD of hypertension treatment?

Answer 17

A = Angiotensin pathway (ACE Inhibitor or ARB- if ace not tolerated)
B = Beta blocker (doesnt reduce stroke risk)
C = Ca channel blocker
D = Diuretic (Thiazide)

Think about where these work!

Question 18

What is the second line of hypertension treatment?

Answer 18

• Alpha adrenoreceptor agonist / centrally acting sympathetic agents
• K channel agonists
• Aldosterone antagonists

Note;

Minimisation of other medications that may increase hypertension e.g non-steroidal anti inflammatories and oral contraceptives

Question 19

Describe the effect of anti-hypertensive treatments

Answer 19

Drop around 5mmHg

All have side effects

• ACE inhib = dry cough
• Diuretic = frequent urination

Thus compliance is difficult (study had only 5% total compliance and 30% no drugs)

Question 20

What are recent pharmacological approaches;

part 1

Answer 20

1) Combination of drugs; (ACE inhibit, diuretic, statin)

Question 21

What are recent pharmacological approaches;

part 2

Answer 21

2. Anti-Aldosterone Agents
   • Aldosterone synthase inhibitors
   • Mineralocorticoid receptor antagonists (compete with aldosterone
   for binding site)

Question 22

What are recent pharmacological approaches;

part 3

Answer 22

3. Activators of the non-traditional Angiotensin pathways
• Ang 1-7 analogs
• ACE II activators
• AT2 receptor agonists
• MAS receptor agonists

Question 23

What are recent pharmacological approaches;

part 4

Answer 23

4. Inhibitors of the brain RAS pathway

Question 24

What are recent pharmacological approaches;

part 5

Answer 24

5. Vasopeptide inhibitors (leads to increased circulating natriuretic peptide levels) (BNP or ANP)

Question 25

Describe the alternative ANG pathway;

Answer 25

ANG I is converted by ACE2 to ANG 1-9

ANG II is converted by ACE 2 to ANG 1-7

ANG 1-9 can be converted by ACE to ANG 1-7 act on MasR (all these components counteract ANG I and II I.e opposite effects!!!, sort of negative feedback system

ANG I and II are vasoconstrictors and different from ANG 1-9

Question 26

What are four novel new treatments that target autonomic reflexes?

Answer 26

1. Renal denervation
2. Baroreceptor activation
3. Carotid body ablation
4. Vagal activation

Question 27

Describe a simplicity catheter;

Answer 27

1. Renal nerve ablation

Uses a radio frequency to burn a hole in the renal nerve
Dont need anaesthetic!

Effects described in the previous lecture!

Question 28

What else was very beneficial about the simplicity catheter?

Answer 28

They found that the SNA spillover to the kidney was reduced also to the plasma levels (potentially to the entire systemic too)

May be caused by the loss of afferent feedback

Question 29

/What did caroyln find in terms of cutting renal nerves

Answer 29

That the cutting of renal nerves resulted in less sympathetic nerve loss in rat MI (loss here due to NE toxicity)

Question 30

Does renal denervation work for everyone?

Answer 30

No, in premenopausal women it results in increasing blood pressure. (should only target people who have high renal SNA)

Potential also because of physician poor training.

Question 31

What is another clinical trial that is looking more promising?

Answer 31

Baroreceptor stimulation using a pacemaker,

Stimulation of the carotid sinus nerve results in decreased blood pressure as the body thinks blood pressure is higher than it is.

Unsure about long term effects