Renin-angiotensin System Flashcards
Physiology of RAAS
- regulation of BP
- regulation of plasma volume
- modulation of sympathetic nervous system
- stimulation of thirst
Where is renin formed and stored?
JG cells
What is the primary regulator of formation and maintenance of Ang II?
Renin
Is Ang I active or inactive?
Inactive
Is Ang II active or inactive?
Active
What does ACE do?
- convert Ang I to Ang II
- breakdown bradykinin to inactive metabolites
Bradykinin can cause what?
- vasodilation (cough, angioedema)
- decrease MAP
Ang II AT1 causes what?
- vasoconstriction (increased TPR, Increased MAP)
- aldosterone release (Na and water retention, increased MAP)
Level of Ang II is dependent on what?
Amount of circulating renin and angiotensinogen
Angiotensinogen is formed and secreted continuously by what?
Liver
Synthesis of angiotensinogen is increased by what?
Insulin
Estrogens
Glucocorticoids
Renin is secreted from ____ in response to changes in ____
Kidney
BP/volume
What is the clinical test for renin activity? What is the relationship with dietary Na?
PRA
Inverse relationship with dietary Na intake
Renin secretion is regulated by (3)
- Blood volume/pressure (baroreceptors)
- Na Cl flux across macula
- Sympathetic nervous system activity
Baroreceptors and renin
Decreased bp/volume —> decreased stretch —> increased renin
The macula densa is sensitive to what changes?
NaCl reabsorption
Macula densa and renin
Decrease NaCl reabsorption —> increase renin
Stimulation of what receptors on JG cells cause renin release
B1
SNS activity and renin
Increase SNS activity —> increase renin release
What are the 2 negative feedback loops of renin?
- Ang II stimulation of AT1 receptors on JG cells (short)
2. Ang II induced increases in BP (long)
How is Ang I formed?
Angiotensinogen —> Ang I
**renin RLS
Where is ACE found?
On endothelial cell surface
What is the major active component of RAS?
Ang II
Ang II and K
Increase excretion of K
Ang II and afferent arteriole
Constrict —> decrease glom pressure —> decrease GFR
Ang II and efferent arteriole
Constrict —> increase glomerular pressure —> increase GFR
Normal conditions of Ang II and GFR
Afferent constricts slightly more than efferent
**no change or slight decrease GFR
Renal arterial hypotension and Ang II
Afferent is maximally dilated
GFR maintained by Ang II mediated constriction fo efferent
T/f you can 100% inhibit ACE
False!
There are alternative pathways for ang II synthesis that do not involve renin or ACE
How does Ang II alter cardiovascular structure?
AT1 receptor activation
Ang II VT1 activation
- stimulate migration, proliferation and hypertrophy of VSM cells
- increased production of extracellular matrix
- hypertrophy of cardiac myocytes
2 major subtypes of Ang II
AT1 (Gq)
AT2 (Gi)
Which receptors mediate most biological effects of Ang II?
AT1
Where are Ang II AT1 receptors found?
VSM
Where are AngII AT2 receptors found?
Fetal tissue
What receptor are poorly defined and may exert antiproliferative, proapoptotic, vasodilatory and antihypertensive effects?
AT2
What is the prototype ACEI?
Captopril
