23- RAS, Vaso, and Kinins Flashcards
1
Q
cyclic AMP (cAMP)
A
-activated by AVP activation of V2 receptors
2
Q
aldosterone
A
- hormone produced and secreted by adrenal cortex
- secreted in response to activation of RAS (Ang-II and III) and functions to inc. retention of Na and water to inc. blood pressure
3
Q
angiotensin
A
-peptides that are formed by combined proteolytic actions of renin and angiotensin converting enzymes [Ang-I, Ang-II, Ang-III, and Ang-(1-7)]
4
Q
angiotensin converting enzyme (ACE)
A
- enzyme (ACE1) that converts Ang-I to various active peptides (Ang-II, Ang-III) that have cardioregulatory effects
- part of classical RAS pathway that can mediate hypertension
5
Q
ACE2
A
- enzyme that converts angiotensin I and II to alt. peptide Ang-(1-7) which interacts with Mas receptor
- this ACE2-Ang-(1-7)-Mas pathway is counterregulatory to classical RAS pathway and has cardioprotective effect
6
Q
angiotensinogen
A
- large peptide that is activated by renin secreted from kidneys to form Ang-I
- initial inactive peptide of RAS pathway
7
Q
Ang-(1-7)
A
- created by ACE2 conversion of Ang-I or Ang-II
- interacts with Mas receptor to dec. blood pressure and cause naturesis
8
Q
AT1 receptor
A
- predominate receptor of RAS and mediates most actions of Ang-II and Ang-III
- stimulates phospholipase C (PLC) which inc. intracellular Ca++ and MAPK
- Ca mediates vasoconstrictive effects
- MAPK causes cardiac remodeling
- because AT1 levels > AT2, AT1 effects normally predominate
- target of ARBs
9
Q
AT2 receptor
A
- stimulate inc. in NO release and block MAPK activation
- mediates vasodilation and natriuresis
- opposes AT1 mediated vasoconstriction and may be important with AT1 blockade
- normally AT1 receptor levels > AT2 levels so AT1 effects normally predominate
10
Q
Mas receptor
A
- mediates vasodilation, anti-inflammation, anti-cell proliferation opposes AT1 receptor-mediated effects
- stimulates inc. Ca and NO release
- activation opposes effects of classical RAS pathway
11
Q
eicosanoids
A
-release mediated by bradykinin activation of PLA2, which stimulates vasodilation
12
Q
juxtaglomerular cells (JG cells)
A
-stimulated by SNS to release renin when there is a decrease in blood pressure detected by systemic baroreceptors or inc. renal nerve activity
13
Q
kininase II
A
-enzyme that creates bradykinin from kininogen/kallikrein
14
Q
kininogen/kallikrein
A
- precursors to bradykinin
- bradykinins are vasodilator peptides
- broken down by kinase II (ACE1)
- ACE inhibitors prevent breakdown and cause dry cough
15
Q
phospholipase A2 (PLA2)
A
- activated by bradykinin binding to B2 receptor
- causes release of eicosanoids (i.e. prostaglandins) which mediates dilation
16
Q
phospholipase C (PLC)
A
- activated by AT1 receptor and causes release of Ca (vasoconstriction) and MAPK (cardiac remodeling)
- also modulates inc. Ca++ when bradykinin binds to B2 which inc. pain, contraction, and NO
17
Q
renin
A
- enzyme secreted by the kidneys in response to:
1. dec. stretch of renal vessels
2. dec. Na in macula densa
3. SNS stimulation of juxtaglomerular cells - release inhibited by: Ang-II, AVP, high K
- those on ACEI and ARBs lose feedback inhibition
18
Q
candesartan
A
AT1 antagonist (ARB)
- primarily used from HTN and heart failure
- lack some side effects of ACE inhibitors– for patients that don’t tolerate ACE inhibitors
- higher affinity for AT1 receptors than AT2 receptors
- Do NOT affect kininase II
- still allow for AT2 activation and may increase production of Ang-(1-7)
- blocking AT1 results in loss of AII feedback inhibition of renin release (increased release of renin leading to AI and AII being metabolized to Ang-(1-7) by ACE2)
- side effects- hypotension, hyperkalemia, acute renal failure in patients with renal insufficiency
- Contraindicated in pregnant and nursing mothers
19
Q
irbesartan
A
AT1 antagonist (ARB)
- primarily used from HTN and heart failure
- lack some side effects of ACE inhibitors– for patients that don’t tolerate ACE inhibitors
- higher affinity for AT1 receptors than AT2 receptors
- Do NOT affect kininase II
- still allow for AT2 activation and may increase production of Ang-(1-7)
- blocking AT1 results in loss of AII feedback inhibition of renin release (increased release of renin leading to AI and AII being metabolized to Ang-(1-7) by ACE2)
- side effects- hypotension, hyperkalemia, acute renal failure in patients with renal insufficiency
- Contraindicated in pregnant and nursing mothers
20
Q
losartan
A
AT1 antagonist (ARB)
- primarily used from HTN and heart failure
- lack some side effects of ACE inhibitors– for patients that don’t tolerate ACE inhibitors
- higher affinity for AT1 receptors than AT2 receptors
- Do NOT affect kininase II
- still allow for AT2 activation and may increase production of Ang-(1-7)
- blocking AT1 results in loss of AII feedback inhibition of renin release (increased release of renin leading to AI and AII being metabolized to Ang-(1-7) by ACE2)
- side effects- hypotension, hyperkalemia, acute renal failure in patients with renal insufficiency
- Contraindicated in pregnant and nursing mothers
21
Q
valsartan
A
AT1 antagonist (ARB)
- primarily used from HTN and heart failure
- lack some side effects of ACE inhibitors– for patients that don’t tolerate ACE inhibitors
- higher affinity for AT1 receptors than AT2 receptors
- Do NOT affect kininase II
- still allow for AT2 activation and may increase production of Ang-(1-7)
- blocking AT1 results in loss of AII feedback inhibition of renin release (increased release of renin leading to AI and AII being metabolized to Ang-(1-7) by ACE2)
- side effects- hypotension, hyperkalemia, acute renal failure in patients with renal insufficiency
- Contraindicated in pregnant and nursing mothers
22
Q
captopril
A
ACE inhibitor
- uses: HTN, LV systolic dysfunction, MI, heart failure
- BP loweing effects may be mediated by increased production of Ang-(1-7)
- side effects- DRY COUGH, angioedema (d/t bradykinin) hypotension, hyperkalemia, acute renal failure in renal insufficiency
- Contraindicated in pregnant and nursing mothers
23
Q
enalapril
A
ACE inhibitor
- uses: HTN, LV systolic dysfunction, MI, heart failure
- BP loweing effects may be mediated by increased production of Ang-(1-7)
- side effects- DRY COUGH, angioedema (d/t bradykinin) hypotension, hyperkalemia, acute renal failure in renal insufficiency
- Contraindicated in pregnant and nursing mothers
24
Q
lisinopril
A
ACE inhibitor
- uses: HTN, LV systolic dysfunction, MI, heart failure
- BP loweing effects may be mediated by increased production of Ang-(1-7)
- side effects- DRY COUGH, angioedema (d/t bradykinin) hypotension, hyperkalemia, acute renal failure in renal insufficiency
- Contraindicated in pregnant and nursing mothers
25
Q
conivaptan (Vaprisol)
A
Vasopressin receptor antagnoist
- V1 and V2 receptor antagonist
- Tx of hyponatremia 2/2 SIADH
- available as IV drug.
26
Q
tolvaptan (Samsca)
A
Vasopressin receptor antagnoist
- Selective V2 receptor antagonist.
- Tx of hypervolemic and euvolemic hyponatremia that is resistant to fluid restriction (ie HF, cirrhosis, SIADH).
- PO preparation
27
Q
aliskiren (Tekturna)
A
Renin inhibitor
- used for essential HTN
- S/E: same as ARB’s and ACEI with addition to GI and allergic Sx.
- Not as effective for pt with HTN and low renin levels.
