Renin-Angiotensin System Flashcards
Describe the Steps of the Renin Angiotensin System
- Angiotensionegen → Angiotensin I (Renin)
- Angiotensin I → Angiotensin II (ACE)
- Angiotensin II binds Angiotensin II receptors
- Angiotensin II receptors cause release of Aldosterone
- Blood Pressure Regulation
Juxtaglomerular apparatus (macula densa, sympathetic nerves)
Renin containing cells
- Macula Densa - specialized epithelial cell
- Sympathetic nerves - Afferent arteriole
3 Primary mechanisms of Renin release
- Intrarenal baroreceptor - stretch/renal perfusion pressure (decreased pressure increase renin)
- Macula densa - sodium load (decrease salt increase renin)
- β-adrenergic receptor - Sympathetic nerves (If blocked, decrease renin)
Angiotensin II effect on Renin release
- Angiotensin II causes feedback inhibition
- Suppresses renin release by direct action on JG cells
Different roles of Angiotensin receptors (AT1)
AT1
- Vasoconstriction
- Vascular proliferation
- Aldosterone secretion
- Cardiac myocyte proliferation
- Increased sympathetic tone
Different roles of Angiotensin receptors (AT2)
AT2
- Vasodilation
- Antiproliferation
- Apoptosis
Mechanism of action for AT1 receptor
- Angiotensin II binds AT1
- Gq → PLC
- PLC → IP3 and DAG
- IP3 leads to release of Ca2+
AT1 receptor effects on vascular smooth muscle
- Arterial vasoconstrictor - increase BP
- Hypertrophy - increase in wall to lumen ratio
- Increase extracellular matrix proteins such as collagen
AT2 receptor effects on vascular smooth muscle
- Endothelium-dependent vasodilation (NO mediated)
- Inhibition of proliferation of smooth muscle
- Promotes apoptosis
How does the adrenal cortex promote sodium reabsorption
Stimulates aldosterone biosynthesis and secretion via AT1 receptor
Effects of aldosterone are blocked by ______ and ______
Spironolactone; Eplerenone
Actions of Angiotensin on CNS
- Promotes thirst-dipsogenic
- Promotes ADH release
- Promotes positive water balance
Angiotensin actions on Sympathetic Nervous System
- Facilitates norepinephrine release
- Inibits norepinephrine reuptake
- Promotes epinephrine secretion from adrenal medulla
Angiotensin Actions on the Heart
- Hypertrophy of cardiac myocytes
- Increase in extracellular matrix production of fibroblasts
Mechanism of action for Aldosterone
- Specific mineralcorticoid receptor agonist
- Activates expression of target genes involved in sodium reabsorption and potassium secretion
Where in the kidney does Aldosterone act?
Principal cells of the collecting duct
Aldosterone actions of Heart
- Fibrosis (both ventricles)
- Left ventricular hypertrophy
Renin Angiotensin System pathology (Hypertension) - 2 methods
- Angiotensin II leads to:
- vasoconstriction ⇒ increases BP
- Aldosterone ⇒ increases BP
Renin Angiotensin System Pathology (CHF)
-
Vasoconstriction increases afterload
- affects sympathetic nervous system
- Arrhythmia
- Promotes myocardial hypertrophy and apoptosis
- Aldosterone increases pre-load (fibrosis and LVH)
Types of Renin Angiotensin System inhibitors
- AT1receptor blocker
- ACE inhibitor
- Renin inhibitor
Losartan
Competitive angiotensin receptor antagonist - selective for AT1
Losartan
Adminstration:
Use:
Administration: Orally active
Use: Treatment of essential HTN
Losartan - Reduction of Blood Pressure
Reduces blood pressure without increasing heart rate
- Should be used w/ caution in patients with volume depletion
- Diuretics enhance action
- Renal failure may decrease in patients with CHF or renal artery stenosis
Losartan - Improvement of HF
- Decreases BP (afterload)
- Reduces left ventricular filling pressure
- Decreases aldosterone - reduces sodium retention, fibrosis and hypertrophy (decreases preload)
Losartan is contraindicated in ______
Side Effects:
Pregnancy
Side Effects: Dizziness, cough, angiodema
ACE inhibitors
- Captopril
- Enalapril
- Lisinopril
Direct action of ACE Inhibitors
- Block angiotensin II formation and bradykinin degradation
ACE Inhibitors
Administration:
Use:
Side Effects:
Administration: Orally active
Use: Essential HTN related to renin activity
Side Effects: rash, proteinuria, and neutropenia occur with captopril (cough and angiodema may occur)
ACE Inhibitors - Reduction of BP
Reduce BP without Increasing HR
- Should be used with caution in volume depleted patients
- Diuretics enhance action
ACE Inhibitors - Improvement of HF
- Decreases BP (Afterload)
- Reduces left ventricular pressure
- Increases cardiac output
- Decreases aldosterone (Preload)
Enalapril and lisinopril are ________
pro-drugs
Enalapril → Enalaprilate (Active)
Lisinopril → Lisinoprilate (Active)
Aliskiren
Renin inhibitor
Aliskiren
Administration:
T1/2:
Use:
Administration: Orally Active
T1/2: 24 hours - given once daily
Use: Treat HTN (lowers BP with no change in HR)
Aliskiren HTN effects
- HTN effects related to pretreatment plasma renin activity
- Enhanced by Diuretic, ACE inhibitor or AT1 blocker
- Decrease plasma angiotensin II and aldosterone
