Vascular Endothelium Flashcards

1
Q

What are the functions of the endothelial layer

A
Vascular tone
Thrombostasis
Absorption and secretion
Barrier
Growth
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2
Q

How does the endothelial layer contribute to vascular tone, thrombostasis and growth

A

Secretes and metabolises vasoactive substances

Prevents clots forming or molecules adhering to the vessel wall

Mediates cell proliferation

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3
Q

How is the endothelial layer involved in absorption and secretion

A

Allows active/passive transport via diffusion/channels

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4
Q

How does the endothelial layer at as a barrier

A

Prevents atheroma development and impedes pathogens

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5
Q

Give some mediators of the endothelium

A
Nitric Oxide
Prostacyclin
Thromboxane
Endothelin-1
Angiotensin II
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6
Q

Describe the synthesis pathway of prostacyclin and thromboxane

A
  1. Phospholipids converted to arachidonic acid by Phospholipase A
  2. Arachidonic acid converted to prostaglandin precursor by cyclooxygenases (COX1, COX2)
  3. Prostacyclin and thromboxane formation
  4. Formation of PGD2, PGE2, PGF2

Can also be synthesised from DAG by DAG lipase

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7
Q

How does aspirin work

A

Inhibits cyclooxygenase enzymes (COX1, COX2) and therefore reduces thromboxane formation
Reduces pain, fever, inflammation

COX1 - aspirin acetylation inactivates the enzyme
COX2 - aspirin acetylation switches function to generate protective lipids

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8
Q

What is an unwanted effect of aspirin

A

Disables prostacyclin which is a vasodilator, anti-atherogenic and anti-platelet

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9
Q

Describe the synthesis pathway for NO

A
  1. ACh binds to a G-protein coupled receptor
  2. Phospholipase C activated
  3. PIP2 converted to DAG and IP3
  4. Stimulation of calcium release from the SR
  5. Calcium up regulates eNOS
  6. eNOS converts L-Arg and oxygen to L-Cit and NO
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10
Q

Describe how prostacyclin causes relaxation

A
  1. PGI2 is produced via COX1
  2. PGI2 diffuses into the VSMC and binds to an IF receptor
  3. Upregulation of adenyl cyclase
  4. AC converts ATP to cAMP
  5. cAMP inhibits myosin light chain kinase
  6. Reduced cross bridges
  7. Relaxation
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11
Q

Where is prostacyclin found in abundance

A

Endothelial cells rather than platelets

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12
Q

Describe how thromboxane A2 causes constriction

A
  1. TXA diffuses through the apical and basement membrane
  2. TXA binds to TP On the VSMC
  3. PLC migrates along the membrane
  4. PLC converts PIP2 to IP3
  5. IP3 triggers calcium influx
  6. VSMC contracts
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13
Q

What is the effect of TXA on platelets

A

TXA binds to TP receptors on platelets
Platelets become active to produce more TXA
Positive feedback

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14
Q

Describe the synthesis pathway for angiotensin II and its effect

A
  1. Liver produces angiotensinogen
  2. Renin from the kidney cleaves angiotensinogen into angiotensin I
  3. Angiotensin converting enzyme from endothelial cells convert this to angiotensin II
    4 Increased water retention
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15
Q

Describe how angiotensin II leads to contraction

A
  1. angiotensin II diffuses across the endothelium
  2. Angiotensin binds to the AT1 receptor
  3. PLC migrates along the membrane
  4. PLC converts PIP2 to IP3
  5. IP3 causes calcium influx
  6. Calcium up regulates myosin light chain kinase
  7. Cell contracts
  8. ACE metabolises bradykinin -> no relaxation
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16
Q

What are the effects of angiotensin II

A
Vasopressin secretion
Aldosterone secretion 
Tubular sodium reabsorption 
Sympathoexcitation
Arteriolar vsaoconstriction
17
Q

Describe the synthesis pathway for endothelin 1

A
  1. Endothelial nucleus produces big endothelin 1

2. Endothelin converting enzyme converts zymogen to ET-1

18
Q

How does NO cause vasodilation

A
  1. NO diffuses out the lungs into the VSMC to activate guanylyl cyclase
  2. Guanylyl cyclase converts GTP to cGMP to up regulate PKG
  3. PKG causes potassium efflux
  4. Membrane hyperpolarises
  5. Vessel relaxes and dilates
19
Q

Describe how endothelin 1 works

A
  1. ET-1 binds to ET and Ets receptors on VSMC
  2. PLC converts PIP2 to IP3
  3. IP3 triggers calcium influx
  4. Cell contracts
  5. ET-1 binds to ETB on endothelila cells
  6. Increased NO production
  7. NO diffuses into VSMC
  8. Cell relaxes
20
Q

What do NSAIDs do

A

Causes reversible inhibition of COX

21
Q

What does bradykinin do

A

Causes NO mediated vasodilation/relaxation

22
Q

What do calcium channel blockers do

A

Calcium channel blockers prevent calcium entering VSMCs

23
Q

What do nitrovasodilators do

A

Nitrovasodilators donate exogenous NO, causing vasodilation

24
Q

What are the antagonists for endothelin-1 synthesis

A
PGI2
NO
ANP
heparin
HGF
EGF
25
Q

What are the agonists for endothelin-1 synthesis

A

Adrenaline
ADH
Ang II
IL-1