RAS, vasopressin, and kinins Flashcards
Angiotensin II interacts with _____ receptors and angiotensin III interacts with ______ receptor
AT1/2
AT1
which receptor produces HTN, stroke, CV events
ACE-AII-AT1
Mas receptor p’way
alternative processing of AI and AII by ACE2 or endopeptidases leads to to the alt peptide Ang 1-7
Mas comprises a counterregulatory, cardioprotective branch of the classical RAS p’way
where is ACE1 present
endothelial vascular cells, luminal side
where is renin released
in kidney, by juxtoglomerular apparatus
4 mechanisms that control renin release
- renal vascular receptors in the afferent arteriole (stretch)
- macula densa receptor (increased release w decreased Na)
- SNS. increased renal nerve activity leads to norepi release leads to beta adrenoreceptors on JG leads to increased renin
- AII, vasopressin, K all inhibit release of renin.
why do pt on ACE inhibitors have high renin/AI levels
no fb inhibition from AII. (ACE2 is insensitive to ACE inhibitors)
what stimulates renin release
- decreased arterial pressure (via renal baroreceptors and systemic baroreceptors)
- dehydration/hemorrhage (barorecptors in atrium, ventricle, and pulm veins response to decreased BV; chemoreceptors in hypothalamus also respond)
- hyponatremia (sensed by macula densa)
how does angiotensin raise BP (4 actions)
- direct vasoconstriction via AT1 receptors presens on smooth muscle (increase Ca) & slow pressor effect independent of this action
- in CNS, increase SNS activity and vasopressin release
- in PNS, stimulation of norepi release from symp neurons
- adrenal medulla: stim release of epi
other CV effects of angiotensin
- increases HR and contractility, but often offset by the baroreflex
- hypertrophy/tissue remodeling by both non hemodynamic and hemodynamic mechanisms. nonhemodynamic mechanisms involve direct actions of these peptides on vascular smooth muscle cell growth
central actions of angiotensin
- stimulates drinking and increases secretion of ACTH and vasopressin (more angio II than III, much more potent)
- ACTH stimulates synthesis/release of aldosterone (actions of AII/AIII equal here)
renal actions of angiotensin
promotes sodium retention by vasoconstriction and increasing prox tubular Na reabsorption, regulates own production by inhibition to renin release
AT1 receptor
G-pro coupled receptor, most actions of AII, AIII are believed to be mediated by this receptor
-stimulates phospholipase C to increase Ca, causes constriction and increases MAPK (proliferative responses, like hypertrophy and tissue remodeling)
AT2 receptor
- does not activate phospholipase C or Ca signaling, but stimulates increases in NO and blocks MAPK activation.
- vasodilation and natriuresis
- opposes AT1 -medicated vasoconstriction and may be important in effects of AT1 receptor blockers. AT1 > AT2 in blood vessels.
Mas
mediates vasodilation, anti-inflammation, anti-cell proliferation opposes AT1 receptor mediated effects. increases Ca/NO
losartan
ARB (AT1 receptor blocker)
- primarily used for HTN, HF
- potent non-peptide competitive antagonist of AT1 receptors w high specificity
- lack some SE of ACE inhibitors, considered for patients that don’t tolerate ACE inhibitors
- higher affinity for AT1 than 2 or Mas
- don’t affect kininase II (enzyme that degrades bradykinin, identical to ACE)
- BP lowering may be medicated in part by residual AT2 receptor activation
valsartan
ARB (AT1 receptor blocker)
- primarily used for HTN, HF
- potent non-peptide competitive antagonist of AT1 receptors w high specificity
- lack some SE of ACE inhibitors, considered for patients that don’t tolerate ACE inhibitors
- higher affinity for AT1 than 2 or Mas
- don’t affect kininase II (enzyme that degrades bradykinin, identical to ACE)
- BP lowering may be medicated in part by residual AT2 receptor activation
candesartan
ARB (AT1 receptor blocker)
- primarily used for HTN, HF
- potent non-peptide competitive antagonist of AT1 receptors w high specificity
- lack some SE of ACE inhibitors, considered for patients that don’t tolerate ACE inhibitors
- higher affinity for AT1 than 2 or Mas
- don’t affect kininase II (enzyme that degrades bradykinin, identical to ACE)
- BP lowering may be medicated in part by residual AT2 receptor activation
irbesartan
ARB (AT1 receptor blocker)
- primarily used for HTN, HF
- potent non-peptide competitive antagonist of AT1 receptors w high specificity
- lack some SE of ACE inhibitors, considered for patients that don’t tolerate ACE inhibitors
- higher affinity for AT1 than 2 or Mas
- don’t affect kininase II (enzyme that degrades bradykinin, identical to ACE)
- BP lowering may be medicated in part by residual AT2 receptor activation
role of Ang-(1-7) in ARB use
-BP lowering effects of ARBs may be mediated in part via increased prod of Ang-(1-7)
SE of ARBs
-hypotension, hyperkalemia, ARF (esp in patients w renal insufficiency, AII/AIII maintain GFR). contraindicated in pregnant/nursing mothers
captopril
ACE inhibitors
uses: antihypertensive (esp essential HTN), LV systolic dysfuntion (reduces mortality), MI (reduces mort), HF (reduces mort)
enalapril
ACE inhibitors
uses: antihypertensive (esp essential HTN), LV systolic dysfuntion (reduces mortality), MI (reduces mort), HF (reduces mort)
lisinopril
ACE inhibitors
uses: antihypertensive (esp essential HTN), LV systolic dysfuntion (reduces mortality), MI (reduces mort), HF (reduces mort)
