Targets of the RAAS

Question 1

How does angiotensin II evoke SM contraction?

Answer 1

Acts on AT-1 receptors (GPCR), (Gq?) evokes calcium release

Question 2

What will cause renin release? (overview but good reminder)

Answer 2

Decreased NaCl sensed by macula densa, decreased BP by decreased stretch in AA’s, and SNS ( includes beta adrenergic receptor agonists)

Question 3

Angiotensin 2 effects

Answer 3

vascular growth
Vasoconstriction- directly and indirectly by causing more noradrenaline release
Salt retention: increased aldosterone and proximal tubule salt absorption

Question 4

Serial cleavage of angiotensin

Answer 4

renin cleaves
ACE cleaves 2 amino acids
1 more is 3
1 more is 4

Question 5

Aldosterone release and action

Answer 5

Due to A2 and A3. (due to AT-1 stimulation)
Also due to high potassium

Causes ENac and ATPase insertion in distal tubule cells to reabsorb sodium and secrete K+

Question 6

ACE inhibitors (example, mechanism, adverse effects)

Answer 6

Cilazipril

mimics angiotensin 1 and stops conversion. Decrease in AII. BINDS TO ACE

ACE also degrades bradykinin, so blocking ACE will increase bradykinin leading to dry cough and angioedema.

Question 7

ACE-I induced angioedema

Answer 7

Affects lips, larynx and pharynx
will cause vasodilation and increased permeability
Also inflammatory. can thus block bradykinin or decrease bradykinin production

Question 8

ARB’s (example, mechanism)

ACE-I or ARBs

Answer 8

Losartan

Competitive antagonists for AT-1 receptor, will thus block most of RAAS

ACE-s more effective but more likely to show adverse effects. ARB as a substitute. Combination therapy is bad due to hyperkalaemia

Question 9

Aldosterone antagonists

Answer 9

spironolactone, potassium sparing diuretic. blocks Mc receptor

Question 10

Calcium channel blockers

Answer 10

As it blocks calcium channels, will decrease vasoconstriction and BP

egs are verapamil (phenylalkamine) and nifedipine/felodipine (for BV’s)

Question 11

Diuretics

Answer 11

Amiloride: blocks ENac
Thiazides: block a Na+/Cl- symport (can casue hypokalaemia)

Question 12

Beta blockers

Answer 12

act mainly on SNS, but this will affect RAAS
Competitive antagonists for for B adrenergic receptors, mainly B1
So will decerase cardiac contractility, and will decrease renin secretion

metoprolol