Lecture 32: Vasoactive Peptides and Inhibitors, The Renin Angiotensin Aldosterone Syndrome Flashcards
What is the rate limiting step of the RAAS pathway?
Renin
What causes renin release?
What causes renin release?
What kind of compound is angiotensin?
A protein or polypeptide
What turns off renin activity?
- Angiotensin II binding to its receptors
- angiotensin II floating around blood will turn off renin production
- negative feedback loop with angiotensin II
What are the two receptors for Angiotensin II?
- AT1 subtype
2. AT2 subtype
What are the key characteristics of AT1 subtype?
One of the two subtypes of angiotensin II receptors
Primarily responsible for vasoCONSTRICTION
GPCR (G protein coupled receptor)
Concentrated in the following:
i. vasculature
ii. myocardial tissue
iii. renal tissue
What is Losartan?
An antagonist for AT1 subtype
What is the response of angio II binding to AT1?
- Vasoconstriction
- Aldosterone release
- Cell proliferation
- hypertrophy
- matrix deposition (increase in fibrosis)
What are the characteristics of AT2 subtype?
Uterus and fetus is where it is expressed
Constitutively expressed but can be induced
Not sure what this guy does
What type of angiotensin receptor can be induced in expression?
AT2
What is the response of angio II binding to AT2?
- vasoDILATION
- bradykinin, NO and cGMP release
- antiproliferation
- apoptosis
What is the effect of angio II on CNS?
Angio II can access brain regions lacking blood brain barrier
Results in
i. central pressure response resulting from sympathetic activation
ii. Endocrine: release of ADH and ACTH
iii. Behavioral: increases thirst and sodium appetite
Intake and Retention of fluid
What is the effect of angio II on the sympathetic nervous system?
- increases release and decrease uptake of NE from postganglionic neurons
- enhances the sensitivity of target tissues to NE
- Net effect is vasoconstriction
Angiotensin II is synergistic with NE
What is the effect of angio II on the adrenal medulla? Adrenal cortex?
- Release of catecholamines from chromaffin cells
2. Stimulates synthesis and release of aldosterone
What is angiotensin II’s effect on kidney?
- antidiuresis and antinatriuresis
- reduces glomerular filtration
- inhibits renin release (negative feedback)
How does angiotensin II lead to disease?
- can lead to HTN through vasoconstriction (slide 17)
- angiotensin II also has growth factor like effects on cardiac myocytes/smooth cells leading to
i. cell proliferation/apoptosis (slide 18)
ii. HYPERTROPHY
iii. fibrosis in myocytes - Has a pro inflammatory response in vascular tissue
i. impairs endothelial cell function and induces oxidation
Slide 19