Lecture 3 Flashcards
protein
a macromolecule with large AA sequence (50 to several hundred AA)
peptide
a short AA sequence (up to 20-30 AA)
proteolytic enzyme AKA protease AKA peptidase
an enzyme that cleaves peptide bonds in peptides & proteins
chops peptide bonds
receptors
proteins (usually located on the plasma memb) to which ligands bind and cause certain effects
Angiotensinogen
precursor of all angiotensins
inactive
continuously secreted by the liver
Renin
protease that is made by juxtaglomerular cells
converts angiotensinogen to angiotensin I
rxn is a RATE LIMITING STEP
Angiotensin I
inactive
formed in systemic cirulation
ACE (angiotensin converting enzyme)
protease
on endothelial cells and circulating in blood
converts Ang I to Ang II
degrades bradykinin (potent vasodilator peptide) into inactive fragments
Angiotensin II
main active peptide of RAS
formed in systemic circulation
has 2 types of receptors (AT1 is the mediator of pressor effects)
Angiotensin 1-7
*peptide member of RAS
some of its effects are opposite to Ang II effects
*mediated through its own receptor (Mas receptor)
*can be formed from both Ang I or Ang II
*Ang I uses NEP to get to Ang 1-7
*Ang II uses ACE2 to get to Ang 1-7
Regulation of renin release through long-loop negative feedback
- macula densa pathway
- intrarenal baroreceptor pathway
- beta-adrenergic receptor pathway
* *increase in circulating Ang II –> decrease renin release
macula densa pathway
decrease NaCl flux across macula densa
Macula densa senses when the filtrate has low levels of NaCl, then it will stimulate the release of renin
intrarenal baroreceptor pathway
decrease BP in afferent arteriole
beta-adrenergic receptor pathway
activation of beta1-receptors on juxtaglomerular cells
release of renin will be stimulated
short-loop negative feedback of renin release
stim Ang receptors on juxtaglomerular cells –> decrease renin release
long-loop negative feedback of renin release
increase circulating Ang II –> increase BP –> decrease renin release
What kind of receptors are AT1 and AT2 receptors?
G-protein coupled receptors
What does Ang II do to the vasculature when AT1 is stimulated?
vasoconstriction
smooth muscle hypertrophy
What does Ang II do to the adrenal cortex when AT1 is stimulated?
stimulates syn and secretion of aldosterone
What does Ang II do to the adrenal medulla when AT1 is stimulated?
stimulates epinephrine release
What does Ang II do to the kidney when AT1 is stimulated?
efferent arteriole vasoconstriction
inhibition of renin release
increased Na+ reabsorption
What does Ang II do to the heart when AT1 is stimulated?
myocardial hypertrophy
collagen synthesis
What does Ang II do to the brain when AT1 is stimulated?
release of vasopressin (=ADH)
stimulation of thirst and salt appetite
increased central sympathetic outflow
ACE-I MOA
- decreased formation of Ang II
- increased circulating levels of bradykinin
- increased (indirectly) formation of Ang (1-7)
also increase renin levels/activity b/c the negative feedback of Ang II is not functional!
Binds to the binding site of ACE
