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PDA Block 2 > Renin-Angiotensin System > Flashcards

Renin-Angiotensin System Flashcards

1
Q

Describe the Steps of the Renin Angiotensin System

A
  1. Angiotensionegen → Angiotensin I (Renin)
  2. Angiotensin I → Angiotensin II (ACE)
  3. Angiotensin II binds Angiotensin II receptors
  4. Angiotensin II receptors cause release of Aldosterone
  5. Blood Pressure Regulation
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2
Q

Juxtaglomerular apparatus (macula densa, sympathetic nerves)

A

Renin containing cells

  • Macula Densa - specialized epithelial cell
  • Sympathetic nerves - Afferent arteriole
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3
Q

3 Primary mechanisms of Renin release

A
  1. Intrarenal baroreceptor - stretch/renal perfusion pressure (decreased pressure increase renin)
  2. Macula densa - sodium load (decrease salt increase renin)
  3. β-adrenergic receptor - Sympathetic nerves (If blocked, decrease renin)
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4
Q

Angiotensin II effect on Renin release

A
  • Angiotensin II causes feedback inhibition
  • Suppresses renin release by direct action on JG cells
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5
Q

Different roles of Angiotensin receptors (AT1)

A

AT1

  • Vasoconstriction
  • Vascular proliferation
  • Aldosterone secretion
  • Cardiac myocyte proliferation
  • Increased sympathetic tone
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6
Q

Different roles of Angiotensin receptors (AT2)

A

AT2

  • Vasodilation
  • Antiproliferation
  • Apoptosis
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7
Q

Mechanism of action for AT1 receptor

A
  • Angiotensin II binds AT1
  • Gq → PLC
  • PLC → IP3 and DAG
  • IP3 leads to release of Ca2+
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8
Q

AT1 receptor effects on vascular smooth muscle

A
  • Arterial vasoconstrictor - increase BP
  • Hypertrophy - increase in wall to lumen ratio
    • Increase extracellular matrix proteins such as collagen
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9
Q

AT2 receptor effects on vascular smooth muscle

A
  • Endothelium-dependent vasodilation (NO mediated)
  • Inhibition of proliferation of smooth muscle
  • Promotes apoptosis
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10
Q

How does the adrenal cortex promote sodium reabsorption

A

Stimulates aldosterone biosynthesis and secretion via AT1 receptor

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11
Q

Effects of aldosterone are blocked by ______ and ______

A

Spironolactone; Eplerenone

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12
Q

Actions of Angiotensin on CNS

A
  • Promotes thirst-dipsogenic
  • Promotes ADH release
  • Promotes positive water balance
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13
Q

Angiotensin actions on Sympathetic Nervous System

A
  • Facilitates norepinephrine release
  • Inibits norepinephrine reuptake
  • Promotes epinephrine secretion from adrenal medulla
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14
Q

Angiotensin Actions on the Heart

A
  • Hypertrophy of cardiac myocytes
  • Increase in extracellular matrix production of fibroblasts
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15
Q

Mechanism of action for Aldosterone

A
  • Specific mineralcorticoid receptor agonist
  • Activates expression of target genes involved in sodium reabsorption and potassium secretion
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16
Q

Where in the kidney does Aldosterone act?

A

Principal cells of the collecting duct

17
Q

Aldosterone actions of Heart

A
  • Fibrosis (both ventricles)
  • Left ventricular hypertrophy
18
Q

Renin Angiotensin System pathology (Hypertension) - 2 methods

A
  • Angiotensin II leads to:
    • vasoconstriction ⇒ increases BP
    • Aldosterone ⇒ increases BP
19
Q

Renin Angiotensin System Pathology (CHF)

A
  • Vasoconstriction increases afterload
    • affects sympathetic nervous system
  • Arrhythmia
  • Promotes myocardial hypertrophy and apoptosis
  • Aldosterone increases pre-load (fibrosis and LVH)
20
Q

Types of Renin Angiotensin System inhibitors

A
  1. AT1receptor blocker
  2. ACE inhibitor
  3. Renin inhibitor
21
Q

Losartan

A

Competitive angiotensin receptor antagonist - selective for AT1

22
Q

Losartan

Adminstration:

Use:

A

Administration: Orally active

Use: Treatment of essential HTN

23
Q

Losartan - Reduction of Blood Pressure

A

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
24
Q

Losartan - Improvement of HF

A
  • Decreases BP (afterload)
  • Reduces left ventricular filling pressure
  • Decreases aldosterone - reduces sodium retention, fibrosis and hypertrophy (decreases preload)
25
Q

Losartan is contraindicated in ______

Side Effects:

A

Pregnancy

Side Effects: Dizziness, cough, angiodema

26
Q

ACE inhibitors

A
  1. Captopril
  2. Enalapril
  3. Lisinopril
27
Q

Direct action of ACE Inhibitors

A
  • Block angiotensin II formation and bradykinin degradation
28
Q

ACE Inhibitors

Administration:

Use:

Side Effects:

A

Administration: Orally active

Use: Essential HTN related to renin activity

Side Effects: rash, proteinuria, and neutropenia occur with captopril (cough and angiodema may occur)

29
Q

ACE Inhibitors - Reduction of BP

A

Reduce BP without Increasing HR

  • Should be used with caution in volume depleted patients
  • Diuretics enhance action
30
Q

ACE Inhibitors - Improvement of HF

A
  • Decreases BP (Afterload)
  • Reduces left ventricular pressure
  • Increases cardiac output
  • Decreases aldosterone (Preload)
31
Q

Enalapril and lisinopril are ________

A

pro-drugs

Enalapril → Enalaprilate (Active)

Lisinopril → Lisinoprilate (Active)

32
Q

Aliskiren

A

Renin inhibitor

33
Q

Aliskiren

Administration:

T1/2:

Use:

A

Administration: Orally Active

T1/2: 24 hours - given once daily

Use: Treat HTN (lowers BP with no change in HR)

34
Q

Aliskiren HTN effects

A
  • HTN effects related to pretreatment plasma renin activity
  • Enhanced by Diuretic, ACE inhibitor or AT1 blocker
  • Decrease plasma angiotensin II and aldosterone

PDA Block 2 (15 decks)

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