8. Vasodilators (2)

Question 1

What are the three mechanisms of renin secretion?

Answer 1

Detected by volume in central veins and baroreceptors in carotid arteries and aortic arch leading to disinhibition of renal sympathetic nerves

Pressure-sensitive granular cells also respond directly to localised fall in renal arterial pressure by secreting renin

Reduced GFR and delivery of sodium to the macula densa cells

Question 2

What is the action of neuroendocrine RAAS in response to plasma volume?

Answer 2

See slide 6

Question 3

What is the mechanism of action of aldosterone?

Answer 3

Steriod hormone
Regulates gene expression
See slide 7

Question 4

What is vasopressin?

Answer 4

An anti-diuretic hormone

Question 5

What is the mechanism of action of vasopressin?

Answer 5

See slide 8

Question 6

What is the mechanism of action for controlling water permeability of collecting duct?

Answer 6

Vasopressin binds to G protein-coupled V2 receptors on basolateral membrane of prinicipal cells in collecting duct

Leads to migration of vescicles containing preformed water channels to apical membrane

AQP-2 channels released from vesicles and inserted into membrane, increasing water permeability

Channels of AQP -3/-4 already in basolateral membrane allow passage of water into hyperosmolar medullary intersitium

Question 7

How does angiotensin II maintain glomerular filtration?

Answer 7

AngII contracts renal mesangium

AngII also contricts renal efferent arteriole

Question 8

Where is the location of AT1 receptor subtype?

Answer 8

Blood vessels 
Heart 
Kidney
Brain 
Lungs 
Liver
Adrenal and pituary glands

Question 9

What is the function of AT1 subtype?

Answer 9

Vasoconstriction
Cardiac contractility 
Remodelling of heart and vessels 
Release of aldosterone and vasopressin
Drinking/thirst
noradrenaline release
Negative feedback on renin release

Question 10

Where is the location of AT2/

Answer 10

Mainly in brain
Reproductive tissue
Heart and foetal tissue

Question 11

What is the function of the AT2 receptor?

Answer 11

Embryogenesis
Anti-proliferative effects
Vasodilation via bradykinin and nitric oxide release

Question 12

Look

Answer 12

At slide 12

Question 13

What are the actions of ACE inhibitors?

Answer 13

Peripheral vasodilation and decrease in BP
Decrease in aldosterone secretion
Decrease in sympathetic activation
Increase in bradykini/PG vasodilation
Decrease in angiotensin mediated generation of ROS
Decrease glomerular filtration rate
Decrease hypertension related remodelling

Question 14

Give some examples of ACE inhibitors?

Answer 14

Cantopril
Enalapril

More common - longer duration 
Lisinopril
Ramipril
Perindopril
Trandolapril

Question 15

What are clinical uses of ACE inhibitors?

Answer 15

Hypertension
Post-MI especially if associated with ventricular dysfunction
In people at high risk of ischaemic heart disease
Heart Failure
Diabetic nephropathy (especially Type 1)
Progressive renal insufficiency

Question 16

How does abnormal activity of RAAS contribute to development of hypertension?

Answer 16

Sodium retaining effects
Vasoconstrictor effects
Structural remodelling

Question 17

Describe pathophysiology of systolic heart failure?

Answer 17

Reduced cardiac output and blood pressure trigger compensatory activation of RAAS to maintain tisue perfusion, promote remodelling

Progressively inadequate/deleterious

Frequent hospitalisation

Significant morbidity and mortality

Question 18

What are the befenfits of RAAS blockade?

Answer 18

Reduce cardiac afterload
Reduce cardiac preload 
enhance diuresis 
Regress LVH and risk of arrhythmias 
Reduce cardiac work and ischaemia 
Improve cardiac output 
Preserve potassium
Reduce symptoms 
Slow progression, reduce frequency and severity of hospitalisation

Question 19

What are adverse effects of ACEIs?

Answer 19

Dry cough and angiooedema
Acute renal failure 
first dose hypotension 
hyperkalaemia 
Teratogenticity

Question 20

What is angioedema?

Answer 20

Vascular reaction, localised oedema due to dilation and increased permeability of capillaries, development of giant wheel

Question 21

What do ACE inhibitors interact with?

Answer 21

Diuretics
Potassium-sparing diuertics
Hypotensive agents
NSAIDS

Question 22

What are the precautions for use of ACEI?

Answer 22

Low dose when starting - monitor BP and renal function
Avoid starting the drug in eastablished renovascular disease
Watch for K+ rising and avoid potassium supplements and K sparing diuretics
Probably contraindicated in severe aortic stenosis
DO NOT GIVE IF PREGNANCY PLANNED

Question 23

What do ARBs do?

Answer 23

Antagonise effects of AngII at AT1 receptors

Do not prevent metabolism of vasodilator mediators such as bradykinin

Question 24

Examples of ARBs?

Answer 24

Losartan
Irbesartan
Valsartan
Candesartan1

Question 25

When are ARBs used clinically?

Answer 25

Hypertension when intolerant of ACEI
Post MI
Risk of ischaemic heart disease
heart failure 
DM nephropathy 
Progressive renal insuffiency

Question 26

What are contraidications of ARBs?

Answer 26

Similar to ACE inhibitors
Contr-indicated in bilateral renal artery stenosis
Caution in unilateral disease, history of renal impairment or generalised atherosclerosis

Avoid in aortic stenosis

Question 27

What are adverse effects of ARBs?

Answer 27

Similar to ACEIs but does not cause a dry cough

Question 28

Example of dual NEP enzyme?

Answer 28

Entresto