hi everyone., Renin-Angiotensin-Aldosterone system explained in a lucid manner to understand the concept in a better way.

1. Renin-Angiotensin-Aldosterone
System- Drugs Overview.
Dr.THIRIVIKKIRAMAN.Z M.sc (N), M.A
Sociology,Ph.d (N)
Asst.Professor,
INDIRANI COLLEGE OF NURSING,
PUDUCHERRY

2. Renin-Angiotensin-Aldosterone System-
Drugs Overview.
INTRODUCTION
• The RAAS plays an important role in regulating Blood pressure,
Blood Volume &Fluid Electrolyte Balance.
• The RAAS also mediate certain Pathophysiological changes
associated with Hypertension, Heart Failure, & Myocardial
Infarction.
• The RAAS exerts its effects in large part through Angiotensin II.

3. Types of Angiotensin
 The Angiotensin Family consists of :
1) Angiotensin - I
2) Angiotensin - II
3) Angiotensin – III
 All three compounds are small polypeptides.
 Angiotensin I is the precursor of Angiotensin-II and has very little
biological activity.
 But Angiotensin-II has very high biological activity.
 Angiotensin -III which is formed by degradation of Angiotensin-II, has
moderate biologic activity.

4. Angiotensinogen
Angiotensin I
(inactive)
Blood Pressure
Blood volume
Renal Perfusion
Sodium depletion
Beta1 stimulation
REGULATION OF BLOOD PRESSURE BY THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
RENIN
Angiotensin
converting enzyme
(ACE)
Blocked by
ACE inhibitors
ANGIOTENSIN II
(active)
Renal
Vasoconstriction
Renal blood flow
Glomerular filtration
Retention of sodium and water (and loss of potassium)
ALDOSTERONE
Sodium /
Potassium exchange
Blood volume
Blood Pressure
Systemic Vasoconstriction
(arterioles and veins)

5. Actions of Angiotensin – II
• Angiotensin-II mediates essentially all of the effects of
the RAAS.
• The most prominent actions of Angiotensin II are:
1) Vasoconstriction
2) Stimulation of Aldosterone release.
 Both actions serve to raise Blood pressure.
 Angiotensin-II can act on the heart and blood vessels to
alter their morphology.

6. VASOCONSTRICTION
• Angiotensin-II is a potent Vasoconstrictor.
• It acts directly on Vascular Smooth Muscle(VSM) to cause
contraction.
• Vasoconstriction is prominent in Arterioles and less so in
Veins.
• As a result Angiotensin-Induced vasoconstriction, blood
pressure rises.

7. In addition to its direct action on blood vessels,
Angiotensin-II can cause Vasoconstriction indirectly by
acting on
1)Sympathetic Neurons to promote Nor epinephrine
release.
2) The Adrenal Medulla to promote Nor epinephrine
release
3) The Central Nervous System to increase Sympathetic
Outflow to blood vessels.

8. Release of Aldosterone
• Angiotensin-II acts on the Adrenal Cortex to promote
synthesis and secretion of Aldosterone.
• Aldosterone , in turn acts on the kidney to cause retention of
Sodium and excretion of Potassium &Hydrogen.
• Because retention of Sodium causes water to be retained as
well, aldosterone to increase plasma volume and thereby
increases blood pressure.
• The Adrenal Cortex is highly sensitive to Angiotensin-II –As a
result Angiotensin II can stimulate Aldosterone release .

9. • Aldosterone secretion is enhanced when Sodium levels
are low and when Potassium levels are high.

10. Alteration of Cardiac & Vascular Strucutre
• Angiotensin-II may cause Pathologic Structural changes in
the Heart & Blood vessels.
• Angiotensin-II cause both Hypertrophy (Increased mass of
a structure) & Remodeling (redistribution of mass within a
structure).
• In Hypertension, Angiotensin-II may be responsible for
increasing the thickness of blood vessels
• In Atherosclerosis ,Angiotensin-II may be responsible for
thickening the intimal surface of blood vessels.
• In Heart Failure & myocardial Infarction, it may be
responsible for causing cardiac hypertrophy and fibrosis.

11. Formation of Angiotensin II by Renin & ACE
• Angiotensin II is formed through two sequential reactions.
• The first is catalyzed by Renin, the second by ACE.

12. RENIN
 Renin (pronounced “reenin”) catalyzes the formation of
Angiotensinogen
 This reaction is the rate limiting step in Angiotensin II
formation.
 Renin is produced by Juxtaglomerular cells of the Kidney
and undergoes controlled release into the bloodstream ,
where it converts Angiotensinogen into Angiotensin- I.

13. REGULATION OF RENIN RELEASE
 Release of Renin can be triggered by multiple
factors such as:
Reduced Blood Pressure
Reduced Blood Volume
Reduced Plasma Sodium content or Renal perfusion
Pressure

14. Reduced renal Perfusion pressure is an especially
important stimulant for renin release and can occur in
response to
1) Stenosis of the renal arteries.
2) Reduced systemic blood pressure
3) Reduced Plasma volume (Dehydration,hemorhage or
chronic sodium depletion)
 These factors increase renin release through effects
exerted locally in the kidney.

15. • Some of these factors may also promote renin release
through activation of the Sympathetic Nervous System.
• Sympathetic nerves increase secretion of renin by causing
stimulation of Beta1-adrenergic receptors on
Juxtaglomerular cells.

16. Suppression of Renin
• Renin is suppressed by factors opposite to those that
cause release
• Renin secretion is inhibited by
Increased Blood Pressure
Increased Blood Volume
Increased Plasma Sodium content
• Hence further release of Renin is suppressed through the
above factors.

17. Angiotensin-Coverting Enzyme(KinaseII)
• ACE catalyses the conversion of Angiotensin I (Inactive)
into Angiotensin II (highly Active).
• ACE is located on the luminal surface of all blood vessels,
the vasculature of the lungs being especially rich in the
enzyme.
• Because ACE is abundant, conversion of Angiotensin I
into Angiotensin II occurs instantly after Angiotensin I is
formed.

18. • ACE is a relatively nonspecific enzyme that can act on a variety
of substrates in addition to Angiotesnsin II
• NOTE – Nomenclature regarding ACE can be confusing
• ACE can act on several substrates.
• When the substrate is angiotensin I, we refer to the enzyme as
ACE.
• When the ACE enzyme is acting on other substrates, we refer
to it by different names, and when it is a hormone known as
Bradykinin, we Refer to the enzyme as KINASE II
• Hence it is ACE or KINASE II both are same.

19. THANK YOU…