The renin-angiotensin-aldosterone system (RAAS) is a critical regulator of blood volume, electrolyte balance, and systemic vascular resistance. While the baroreceptor reflex responds short term to decreased arterial pressure, the RAAS is responsible for acute and chronic alterations. The classical understanding of RAAS is that it comprises three significant compounds: renin, angiotensin II, and aldosterone. These three compounds elevate arterial pressure in response to decreased renal blood pressure, salt delivery to the distal convoluted tubule, and beta-agonism.

1. Renin Angiotensin System
(RAS) :

2. CONTENT :
1. Introduction :
2. Renin Angiotensin System (RAS) :
3. Mechanism of RAS :
4. Local action of RAS :
5. Drugs Acting on RAS :

3.  Introduction :
 Cardiovascular disease remains the leading cause of
morbidity and mortality so, the renin-angiotensin
system (RAS) has remained a focus of cardiovascular
research for over a century.
 The RAS has been important in physiological
regulation of blood pressure, extracellular volume, and
cardiovascular control of neural and endocrine
function.
 The main physiologically active hormone produced by
this system is, angiotensin (Ang) II produced by the
successive cleavage of angiotensinogen (Agt).
 Abnormal activation of the RAS leads to, development
and progression of numerous cardiovascular diseases
including, hypertension, heart failure, obesity, chronic
kidney disease, coronary artery disease and stroke.
Renin Angiotensin System (RAS) 3

4.  Renin Angiotensin System (RAS) :
Renin Angiotensin System (RAS) 4
 The renin-angiotensin system (RAS) is one of the major control systems which maintain,
blood pressure, body volume and endocrine activities within the body.
 It involves, a cascade of enzymatic reactions that, result in formation of angiotensin II.
Angiotensin II works by modulating vascular tone and body water volume.
 RAS composed of Agt (angiotensinogen), renin, angiotensin-converting enzyme (ACE),
Ang II (angiotensin II) and Ang II receptors (AT1 and AT2 receptors).
1. Angiotensinogen :
 Angiotensinogen synthesized from pre-angiotensinogen (485 AA containing precursor
protein), synthesized by liver.
 It is converted into angiotensinogen, a 452 aa protein that is, secreted into the circulation,
by enzymatic action.
 It is act as, precursor for the formation of Angiotensin II.

5. Renin Angiotensin System (RAS) 5
2. Renin :
Acid protease that, is produced and stored by, secretory
vesicles in the juxtraglomerular cells of the renal medulla.
 It is initially synthesized as a proenzyme, prorenin (406
AA), which is cleaved and released into circulation as active
renin (340 AA).
 Active renin convert angiotensinogen into the angiotensin I
(Decapeptide).
3. Angiotensin II :
 It is the main physiologically active hormone (Octapeptide)
produced by, renin angiotensin system.
It is produced by the successive cleavage of peptides of
angiotensinogen with the help of angiotensin converting
enzyme (ACE) in lung.
 Angiotensinogen act as, precursor for the formation of
angiotensin II.
Fig. No. 2 Juxtraglomerular cells

6. 4. Angiotensin converting enzyme (ACE) :
 It is a peptidase that, catalyses the conversion of Ang I into Ang II.
 It is secreted by the lungs.
 ACE also degrades bradykinin and other vasoactive peptides.
 ACE divide into two subtypes, ACE and ACE2 which are found in various organs.
5. Ang II receptors :
 There are specific receptor for Ang II i.e. AT1 and AT2.
 AT1 : AT1 is a G protein-coupled receptor that, increases the intracellular calcium
concentration. AT1 receptor is the primary target of Ang II, but Ang III also binds.
 AT2 : AT2 is a G protein-coupled receptor that, activates various phosphatases which also
activates membrane potassium channel. AT2 activation triggers the production of nitric
oxide and cGMP.
Renin Angiotensin System (RAS) 6

7.  Mechanism of RAS :
7
Fig. No. 3 Mechanism of Renin-angiotensin system (RAS)
Renin Angiotensin System (RAS)

8. Renin Angiotensin System (RAS) 8

9. 9
Table No. 1 Classical RAS vs Alternative RAS
Renin Angiotensin System (RAS)

10.  Local effect of RAS :
HEART
Myocardial hypertrophy,
inflammation, metabolic changes
and affects cardiac function.
KIDNEY
Nephropathy, fibrosis, cardiac
hypertrophy, inflammation,
vasoconstriction etc.
LUNG
Vascular remolding, endothelial
dysfunction, cell proliferation,
hypoxia, angiogenesis,
inflammation etc.
SKELETAL MUSCLE
Reduce blood flow, inhibit insulin
stimulated glucose uptake, changes
insulin signaling etc.
ADIPOSE TISSUE
Changes lipogenesis and lipolysis,
insulin resistance, increase glucose
reabsorption, obesity etc.

11. BONE MARROW
Promotes development of erythroid
cells, leukemia etc.
BLOOD VESSEL
Vasoconstriction, decreases NO,
endothelial dysfunction etc.
LIVER
Lower insulin sensitivity, fibrosis,
reactive oxygen species (ROS),
inflammation etc.
NERVOUS SYSTEM
Cell death, demethylation,
inflammation, facilitate
phagocytosis etc.
PANCREAS
Reduce blood flow, lower insulin
production, ROS production,
inflammation etc.

12.  Drug acting on RAS :
Renin Angiotensin System (RAS) 12

13. Renin Angiotensin System (RAS) 13

14.  Reference :
1. Rafael Antonio Vargas Vargas, Jesús María Varela Millána, Esperanza Fajardo Bonilla “Renin-
angiotensin system: Basic and clinical aspects-A general perspective” Endocrinología,
Diabetes y Nutrición, 10 May 2021, E-mail address: rvargas3200@hotmail.com
2. Lavoie JL, Sigmund CD. Minireview: Overview of the renin---angiotensin system-an
endocrine and paracrine system. Endocrinology. 2003;144:2179---83,
http://dx.doi.org/10.1210/en.2003-0150.
3. Ichihara A, Kaneshiro Y, Takemitsu T, Sakoda M, Itoh H. The (pro)renin receptor and the
kidney. Semin Nephrol. 2007;27:524---8, http://dx.doi.org/10.1016/j.semnephrol.2007.07.005.
4. K D Tripathi, Essential of Medical Pharmacology, 8th Edition, 2019.
5. H. P. Rang, M. M. Dale, Rang and Dale's Pharmacology, 7th Edition, 2018.
6. https://www.wikipedia.org
7. https://www.google.com
20XX presentation title 14

15. Thank you….