RAS, Vasopressin, Kinins Flashcards
What are some peptides involved in cardiovascular regulation?
angiotensin I
angiotensin II
bradykinin
What are some peptides involved in cardiovascular regulation?
angiotensin I
angiotensin II
bradykinin
What do peptides interact with to control cardiovascular regulation?
effector organs
peripheral nervous system & release of NTs
central nervous system via circumventricular organs
What is the renin angiotensin system (RAS)?
angiotensinogen comes from the liver; protease renin acts on angiotensinogen to clip off first 10 amino acids to form AI; converted to active peptide AII via ACE; converted to AIII by removal of end terminal aspartate; AII & AIII primarily act on ATIreceptor (AII also acts on AT2R)
What are the two pathways of the RAS system that control BP?
classical ACE, AII, AT1R: causes HTN
counter-regulatory ACE2, A1-7, MAS: counteracts HTN
What is renin?
acid protease secreted by kidney; produced by juxtoglomerular apparatus; release leads to HTN (when there is decreased blood flow to the kidney)
Where is ACE found?
on the luminal aspect of epithelial cells of the vascular system
What do ACEIs and ARBs do?
increase counter-regulatory, cardioprotective pathway
What do peptides interact with to control cardiovascular regulation?
effector organs
peripheral nervous system & release of NTs
central nervous system via circumventricular organs
What is the renin angiotensin system (RAS)?
angiotensinogen comes from the liver; protease renin acts on angiotensinogen to clip off first 10 amino acids to form AI; converted to active peptide AII via ACE; converted to AIII by removal of end terminal aspartate; AII & AIII primarily act on AT1receptor (AII also acts on AT2R)
What are the two pathways of the RAS system that control BP?
classical ACE, AII, AT1R: causes HTN
counter-regulatory ACE2, Ang1-7, MAS: counteracts HTN
What is renin?
acid protease secreted by kidney; produced by juxtoglomerular apparatus; release leads to HTN (when there is decreased blood flow to the kidney)
function of Mas receptor
mediates vasodilation, anti-inflammation, anti-cell proliferation; stimulates increase in Ca+2 & NO
What do ACEIs and ARBs do?
increase counter-regulatory, cardioprotective pathway; pts lose all feedback inhibition; renin & AI increase
4 mechanisms that control renin secretion
- -stretch receptors in afferent arteriole respond to decreased stretch for increased renin release
- -macula dense senses decreased Na so increases renin release
- -SNS signals NE release to stimulate beta receptors on juxtaglomerular cells to increase renin release
- -AII, vasopressin, K all inhibit renin release
How does angiotensin raise BP?
direct vasoconstriction; increase SNS activity & increase vasopressin; stimulates NE release from sympathetic neurons in PNS; stimulates release of epi from adrenal medulla
cardiovascular & adrenal actions of AII & AIII
increase BP, increase HR & contractility; hypertrophy & remodeling
increase aldosterone synthesis/release
function of AT1R
mediates most actions of AII, AIII
stimulates phospholipase C to increase Ca+2 (constriction & activation of MAPkinase in remodeling)
function of AT2R
stimulates increase in NO and block MAPK; vasodilation & natriuresis; opposes AT1R-mediated vasoconstriction
function of Mas recpetor
mediates vasodilation, anti-inflammation, anti-cell proliferation; stimulates increase in Ca+2 & NO
mechanism of action of ARBs
competitively antagonize AT1Rs to prevent vasoconstriction & Na retention
residual AT2R activation causes vasodilation & natriuresis
How do ARBs affect renin release?
ARB blockade of AT1Rs results in loss of AII feedback inhibition; renin release is promoted leading to production of more AI & AII; metabolized to Ang1-7 by ACE2
What is the function of the local RAS system?
vascular smooth muscle: local intrinsic control
brain: NT, regulation of SNS, vasopressin release, regulation of arterial pressure & metabolism
What is the cardiovascular action of bradykinin?
vasodilator of arterioles via NO & eicosanoids
*modulates pressure in hypertensive situations but doesn’t contribute to maintenance of basal pressure in normal individuals
What are the two causes of diabetes insipidus?
central DI: gene mutation
nephrogenic DI: receptor mutation
What is vasopressin released in response to?
low arterial pressure
low fluid vol or increased osmolality
pain/nausea/hypoxia
actions of vasopressin
antidiuretic effect: increases permeability of collecting ducts to water at low concentration
direct vasoconstriction: at high concentration
indirect central: acts at area postrema to promote bradycardia
vasopressin receptors
V1: cardiac effects, increase Ca
V2: antidiuretic effects, increase cAMP
