The Renin Angiotensin Andosterone System

RAAS

1. The Renin Angiotensin
Aldosterone System (RAAS)
By: Darya Osman Hussein Daoud

2. Content
What is the Rennin-Angiotensin-Aldosterone System?
Role it plays in Hypertension
Drugs affecting system

3. What is it?
A hormone system
Regulates blood pressure and fluid balance
Involve kidney and Liver

4. Important Factors
Renin
Angiotensinogen
Angiotensin I
Angiotensin II
Aldosterone

5. Renin
A.K.A. Angiotensinogenase
Released from Kidney
Hydrolyzes angiotensinogen

6. Angiotensinogen
Produced and released by liver
Level increased by corticosteroids, estrogen and thyroid hormone
Composed of 453 A.A. but the 1
st
12 are the most important

7. Angiotensin I
Produced in the kidney through action of Renin on Angiotensinogen
Has no biological activity
Precursor to Angiotensin II

8. Angiotensin II
Produced by ACE in lungs
Main hormone responsible for increase in blood pressure
Stimulates Na reabsorption and H+ secretion in proximal tubules of kidney

9. Angiotensin III
Has 40%activity of angiotensin II
Has aldosterone producing activity
Causes increase in mean arterial pressure

10. ACE
Angiotensin Converting Enzyme
Acts in the lungs
Catalyzes conversion of Angiotensin I to
Angiotensin II
Degrades bradykinin and other vasoactive
peptides

12. Types of drugs
I.Angiotensin Converting Enzyme inhibitors (ACE inhibitors)
II.Renin inhibitors
III.Angiotensin II Receptor Blockers (ARBs)
IV.Aldosterone receptor antagonists

13. I. ACE Inhibitors
(Captopril, Enalapril,Lisinopril)
Used as 1
st
line treatment for hypertension in patients with:
High risk of CAD
Diabetes
History of stroke
Heart failure
MI
Chronic kidney disease

14. I. ACE Inhibitors
Action:
Reduce peripheral vascular resistance
No increase in CO,HR or contractility
Cause vasodilation of arterioles and veins
Decrease aldosterone secretion
Reduce cardiac work by decreasing pre and afterload

15. I. ACE Inhibitors
Pharmacokinetics:
Orally bioavailable
Given as drug or prodrug
Captopril and Lisinopril do not require hepatic activation (used in hepatic
impairment)
Fosinopril not eliminated by kidney (used in renal impairment)
Enalaprilat only one given via IV

16. I. ACE Inhibitors
Clinical Use:
Hypertension
Heart failure
Ventricular dysfunction following MI
Diabetic nephropathy

17. I. ACE Inhibitors
Adverse effects:
Hypotension
Dry cough
Angioedema
Renal failure
Skin rash
Hyperkalemia
Altered taste
Teratogenic

18. I. ACE Inhibitors
Advantage
Protect kidneys from kidney damage/failure in
diabetics
Prevent micro-albuminuria

19. II. Renin Inhibitors
Selective inhibitor – Aliskiren
Action:
Lowers BP
Usually used as monotherapy
Side effects:
Causes diarrhea at high doses
Contraindicated in pregnancy
Causes cough and angioedema

20. III. ARBs (Losartan, Valsartan,
Candesartan)
Action:
Lower BP by decreasing vasoconstrictor tone
Mechanism of Action:
Block action of angiotensin II on angiotensin II receptor

21. III. ARBs
Pharmacokinetics
Given orally
T ½ = 1 – 2 hours
Clinical Use
Hypertension
CHF
nephropathy

22. III. ARBs
Adverse Effects
Hypotension
Dizziness
Hyperkalemia (rare)
Special points
No dry cough
No angioedema