Renin/Angiotesnin system Flashcards
What works synergistically with the RAAS?
The SNS
(Increase SNS activity results in increased Renin release, also directly results in increased NaCl reuptake, vasocontriction)
What is the RAAS a critical part of?
The baroreflex system (long term control)
Thus controls blood pressure
How does RAAS control blood pressure?
Alters vascular tone (potent vasocontrictor) Controls natriuresis (NaCL uptake)
RAAS activation does what to blood pressure?
Increases it
Where is renin released?
Renin is released from the juxtaglomerular cells.
What sort of enzyme is renin?
A proteolytic enzyme
What does Renin do?
Converts angiotensinogin into ANG1
What converts ANG1 into ANG2?
ACE
-Cleaves 2 AA
Where is ACE located?
Primarily in endothelial cells (mostly lungs)
What is the effect of ANG2?
Potent vasocontrictor at AT1 receptors
What causes renin release?
Increased Symp
Decreased NaCl past macula dense
Decrease af art bp (renal perfusion pressure)
Beta-agonists
What does ANG2 activation of AT1 result in?
(1) Vascular growth
- Hyperplasia
- Hypertrophy
(2) Vasocontriction
- Direct AT1
- Via increased NE release from SNS
(3) Salt Retention
- Aldosterone secretion when ANG 2 present
- Tubular Na reabsorption
What are agonists that cause smooth muscle contraction?
Hisamine
Angiotensin
NE
All increase Ca influx
What prevents smooth muscle contraction?
Ca channel blockers
What happens beyond ANG2?
ANG2 can be converted into ANG3 and ANG4
One AA cleaved in both cases
What is the function of ANG3?
Promotes aldosterone secretion
What is the function of ANG4?
Inhibition of clot clearance
How many AA is ANG1,2?
10AA
8AA
When is aldosterone released?
Hyperkalemia
ANG2 present
What is the action of aldosterone?
Bind to aldosterone receptor and causes increase apical NA channel expression and increased basolateral Na/K transporters
Increased K secretion
What are drug targets in the RAAS?
ACE inhibitors ARB's (ang recep blockers) (antagonist) Aldosterone antagonists Ca channel blockers Diuretics Beta blockers
Whats an example of an ACE inhibitor?
Ciliazipril
How do ACE inhibitors work?
mimic section of ANG1 that binds to ACE, therefore binds in its place preventing ANG conversion
What is the dual effect of ACE inhibitors?
ACE has similar binding site to Kinase 2.
Kinase 2 is used to degrade bradykinin.
Thus ACE Inhibitors block kinase 2 action also and lead to increased bradykinin levels which has two main symptoms of:
1) Dry Cough
2) Angioedema
What is angioedema?
leakiness of blood vessels in vasodilation in lips, larynx, pharynx (occlude airways)
What is an example of an ARB?
Losartan
What sort of action does an ARBs have?
Competitive reversible antagonist at AT1
Which should be used ARB or ACE inhibitors?
ACE inhibitors are generally more effect.
A combination causes renal damage.
ARB used as substitute for ARB’s
How would you block aldosterone action?
Aldosterone antagonists
Whats an example of an aldosterone antagonist?
Spirinolactone
What does spirinolactone do?
Prevents Na reabsorption caused by aldosterone
How do calcium channel blockers work?
Block channels preventing smooth muscle contraction therefore no change in vasomotor tone and no increase in blood pressure.
Whats an example of a Ca channel blocker?
Verapamil
What do diuretics do?
Oppose ANG2 effects
What is the function of a diuretic primarily/
increases na excretion
Whats an example of a diuretic?
Amilorides
Works by blocking Na channels, therefore no absorption of Na in the kidney
How do beta blockers work?
Competitive antagonists at b adrenergic receptors
primarily B1
What does B blocker use result in?
Decreased contractility
Decreased Renin secretion
Whats an example of a Beta blocker?
Metoprolol
What are three types or diuretics?
Amiloride - blocks Na channels (connecting duct)
Thiazides - Inhibits NaCl transporters
Loop Diuretics - 2ClNaK transporter inhibited
